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Ethanol Intake (ethanol + intake)
Kinds of Ethanol Intake Selected AbstractsAdolescent C57BL/6J (but not DBA/2J) Mice Consume Greater Amounts of Limited-Access Ethanol Compared to Adults and Display Continued Elevated Ethanol Intake into AdulthoodALCOHOLISM, Issue 4 2010Eileen M. Moore Background:, Alcohol use is common during the adolescent period, a time at which a number of crucial neurobiological, hormonal, and behavioral changes occur (Spear, 2000). In order to more fully understand the complex interaction between alcohol use and these age-typical neurobiological changes, animal models must be utilized. Rodents experience a developmental period similar to that of adolescence. Although rat models have shown striking adolescent-specific differences in sensitivity to ethanol, little work has been done in mice despite the fact that the C57BL/6J (B6) and DBA2/J (D2) mice have been shown to markedly differ in ethanol preference drinking and exhibit widely different sensitivities to ethanol. Methods:, The current study examined ethanol intake in adolescent and adult B6 and D2 mice using a limited access alcohol exposure paradigm called Drinking in the Dark (DID). Additionally, the effect of adolescent (or adult) ethanol exposure on subsequent adult ethanol intake was examined by re-exposing the mice to the same paradigm once the adolescents reached adulthood. We hypothesized that adolescent (P25,45) mice would exhibit greater binge-like alcohol intake compared to adults (P60,80), and that B6 mice would exhibit greater binge-like alcohol intake compared to D2 mice. Moreover, we predicted that relative difference in binge-like alcohol intake between adolescents and adults would be greater in D2 mice. Results:, Adolescent B6 mice consumed more ethanol than adults in the DID model. There was no difference between adolescent and adult D2 mice. Conclusions:, This work adds to the literature suggesting that adolescents will consume more ethanol than adults and that this exposure can result in altered adult intake. However, this effect seems largely dependent upon genotype. Future work will continue to examine age-related differences in ethanol intake, preference, and sensitivity in inbred mouse strains. [source] Opioids in the Hypothalamic Paraventricular Nucleus Stimulate Ethanol IntakeALCOHOLISM, Issue 2 2010Jessica R. Barson Background:, Specialized hypothalamic systems that increase food intake might also increase ethanol intake. To test this possibility, morphine and receptor-specific opioid agonists were microinjected in the paraventricular nucleus (PVN) of rats that had learned to drink ethanol. To cross-validate the results, naloxone methiodide (m-naloxone), an opioid antagonist, was microinjected with the expectation that it would have the opposite effect of morphine and the specific opioid agonists. Methods:, Sprague,Dawley rats were trained, without sugar, to drink 4 or 7% ethanol and were then implanted with chronic brain cannulas aimed at the PVN. After recovery, those drinking 7% ethanol, with food and water available, were injected with 2 doses each of morphine or m-naloxone. To test for receptor specificity, 2 doses each of the ,-receptor agonist [d -Ala2,N -Me-Phe4,Gly5 -ol]-Enkephalin (DAMGO), ,-receptor agonist d -Ala-Gly-Phe-Met-NH2 (DALA), or ,-receptor agonist U-50,488H were injected. DAMGO was also tested in rats drinking 4% ethanol without food or water available. As an anatomical control for drug reflux, injections were made 2 mm dorsal to the PVN. Results:, A main result was a significant increase in ethanol intake induced by PVN injection of morphine. The opposite effect was produced by m-naloxone. The effects of morphine and m-naloxone were exclusively on intake of ethanol, even though food and water were freely available. In the analysis with specific receptor agonists, PVN injection of the ,-agonist DALA significantly increased 7% ethanol intake without affecting food or water intake. This is in contrast to the ,-agonist U-50,488H, which decreased ethanol intake, and the ,-agonist DAMGO, which had no effect on ethanol intake in the presence or absence of food and water. In the anatomical control location 2 mm dorsal to the PVN, no drug caused any significant changes in ethanol, food, or water intake, providing evidence that the active site was close to the cannula tip. Conclusions:, The ,-opioid receptor agonist in the PVN increased ethanol intake in strong preference over food and water, while the ,-opioid agonist suppressed ethanol intake. Prior studies show that learning to drink ethanol stimulates PVN expression and production of the peptides enkephalin and dynorphin, which are endogenous agonists for the ,- and ,-receptors, respectively. These results suggest that enkephalin via the ,-opioid system can function locally within a positive feedback circuit to cause ethanol intake to escalate and ultimately contribute to the abuse of ethanol. This is in contrast to dynorphin via the ,-opioid system, which may act to counter this escalation. Naltrexone therapy for alcoholism may act, in part, by blocking the enkephalin-triggered positive feedback cycle. [source] Galanin Knockout Mice Show Disturbances in Ethanol Consumption and Expression of Hypothalamic Peptides That Stimulate Ethanol IntakeALCOHOLISM, Issue 1 2010Olga Karatayev Background:, There is growing evidence suggesting that hypothalamic galanin (GAL), which is known to stimulate intake of a fat-rich diet, has a role in promoting the consumption of ethanol. The present study further examined this possibility in GAL knockout (GALKO) mice. Methods:, Two groups of female and male GALKO mice, compared to wild-type (WT) controls, were trained to voluntarily drink increasing concentrations of ethanol, while maintained on lab chow and water. They were examined in terms of their daily ethanol intake and preference, acute consumption of a high-fat diet, preference for flavored solutions, and expression of different peptides shown to stimulate ethanol intake. Results:, In the GALKO mice compared to WT, the results revealed: (i) a 35 to 45% decrease in ethanol intake and preference, which was evident only at the highest (15%) ethanol concentration, was stronger in female than in male mice, and was seen with comparisons to littermate as well as nonlittermate WT mice; (ii) a 48% decrease in acute intake of a fat-rich diet, again stronger in female than male mice; (iii) no difference in consumption of sucrose or quinine solutions in preference tests; (iv) a total loss of GAL mRNA in the hypothalamic paraventricular nucleus (PVN) of female and male mice; and (v) a gender-specific change in mRNA levels of peptides in the perifornical lateral hypothalamus (PFLH), orexin and melanin-concentrating hormone, which are known to stimulate ethanol and food intake and were markedly decreased in females while increased in males. Conclusions:, These results provide strong support for a physiological role of PVN GAL in stimulating the consumption of ethanol, as well as a fat-rich diet. Ablation of the GAL gene produced a behavioral phenotype, particularly in females, which may reflect the functional relationship of galanin to ovarian steroids. It also altered the peptides in the PFLH, with their reduced expression contributing to the larger behavioral effects observed in females and their increased expression attenuating these effects in males. [source] CB1 Receptor Blockade Decreases Ethanol Intake and Associated Neurochemical Changes in Fawn-Hooded RatsALCOHOLISM, Issue 1 2010Teresa Femenía Background:, This study was undertaken to identify the neurochemical changes underlying the attenuation of voluntary ethanol intake induced by the cannabinoid CB1 receptor antagonist AM251 in fawn-hooded rats. Methods:, Rats were exposed to the 2-bottle-choice paradigm (ethanol 10% v/v or water) for 15 days. After this period, rats received AM251 (3 to 6 mg/kg, i.p.) or vehicle. Results:, Voluntary ethanol intake decreased (30%) with the administration of incremental dosages of AM251 (3 mg/kg, 5 days and 6 mg/kg, 5 days) in rats with acquired high preferring ethanol consumption (>3.5 g of ethanol/kg/d). Ethanol intake significantly decreased proopiomelanocortin expression in the arcuate nucleus (38.31%) and ,-opioid-DAMGO-stimulated [35S]-GTP, binding in the caudate-putamen (40%), nucleus accumbens core (AccC) (32.87%), and shell (AccS) (34.21%). Moreover, ethanol intake increased tyrosine hydroxylase (TH) gene expression in the substantia nigra (24%) and ventral tegmental area (23%) and corticotrophin-releasing gene expression in the paraventricular hypothalamic nucleus (41.6%). The reduction of ethanol intake induced by AM251 was associated with blockade or significant reduction of the changes produced by ethanol in the expression of these genes in key regions related to drug dependence. Interestingly, treatment with AM251 reduced (20%) TH gene expression in rats drinking only water. In this respect, the action of AM251 in reducing TH gene expression may not be specific. Conclusion:, Taken together, these results revealed that blockade of cannabinoid CB1 receptors (CB1r) decreased voluntary ethanol intake in ethanol-habituated rats by normalizing the neurochemical alterations induced by ethanol. [source] Effects of Pregnanolone and Dehydroepiandrosterone on Ethanol Intake in Rats Administered Ethanol or Saline during AdolescenceALCOHOLISM, Issue 7 2009Olga V. Gurkovskaya Background:, Adolescent alcohol use may contribute to long-term changes in the receptors and neuroactive steroids that may mediate its effects and to subsequent alcohol abuse and dependence as an adult. Therefore, in this study, ethanol preference and intake as an adult were examined after adolescent ethanol or saline administration. In addition, ethanol intake in the same groups was examined after administration of 2 neuroactive steroids with modulatory effects at GABAA receptors. Methods:, Two groups of male Long-Evans rats were administered 15 intraperitoneal (i.p.) injections of either ethanol (2 g/kg, 20% v/v) or saline between postnatal days 35 and 63. Starting on postnatal day 75, both groups were trained to consume 10% ethanol using a saccharin-fading procedure, and ethanol intake and preference were measured after a series of manipulations involving food deprivation, changes in the duration of access to ethanol, and changes in the concentrations of ethanol presented. Following these manipulations, pregnanolone (1 to 10 mg/kg) and dehydroepiandrosterone (DHEA, 1 to 100 mg/kg) were administered prior to preference sessions with an 18% ethanol solution. Results:, Adult ethanol preference and intake did not differ significantly in subjects treated with either saline or ethanol as adolescents during training, the substitution of other ethanol concentrations (3.2 to 32%), ad-lib feeding, or moderate food deprivation. Pregnanolone administration altered the intake of both adolescent-treated groups after the first injection of 3.2 mg/kg and after repeated injections with 10 mg/kg, a dose that produced sedation. In contrast, multiple doses of DHEA consistently decreased intake of an 18% ethanol concentration in both groups after repeated injections and 3 doses of DHEA (10, 32, and 56 mg/kg) administered with various ethanol concentrations dose-dependently shifted the ethanol-concentration curves for the volume and dosage of ethanol consumed downward. Conclusions:, These results indicate that chronic intermittent ethanol (CIE) administration of 2 g/kg during adolescence did not alter preference or overall consumption of ethanol in outbred rats trained to drink ethanol as an adult under the conditions tested, and that DHEA may be more effective than pregnanolone at significantly decreasing ethanol consumption. [source] Patterns of Ethanol Intake in Preadolescent, Adolescent, and Adult Wistar Rats Under Acquisition, Maintenance, and Relapse-Like ConditionsALCOHOLISM, Issue 4 2009David García-Burgos Background:, Animal behavioral models of voluntary ethanol consumption represent a valuable tool to investigate the relationship between age and propensity to consume alcohol using an experimental methodology. Although adolescence has been considered as a critical age, few are the studies that consider the preadolescence age. This study examines the ethanol consumption/preference and the propensity to show an alcohol deprivation effect (ADE) after a short voluntary ethanol exposure from a developmental perspective. Methods:, Three groups of heterogeneous Wistar rats of both sexes with ad libitum food and water were exposed for 10 days to 3 ethanol solutions at 3 different ontogenetic periods: preadolescence (PN19), adolescence (PN28), and adulthood (PN90). Ethanol intake (including circadian rhythm), ethanol preference, water and food consumption, and ADE were measured. Results:, During the exposure, the 3 groups differed in their ethanol intake; the greatest amount of alcohol (g/kg) was consumed by the preadolescent rats while the adolescents showed a progressive decrease in alcohol consumption as they approached the lowest adult levels by the end of the assessed period. The pattern of ethanol consumption was not fully explained in terms of hyperphagia and/or hyperdipsia at early ages, and showed a wholly circadian rhythm in adolescent rats. After an abstinence period of 7 days, adult rats showed an ADE measured both as an increment in ethanol consumption and preference, whereas adolescent rats only showed an increment in ethanol preference. Preadolescent rats decreased their consumption and their preference remained unchanged. Conclusions:, In summary, using a short period of ethanol exposure and a brief deprivation period the results revealed a direct relationship between chronological age and propensity to consume alcohol, being the adolescence a transition period from the infant to the adult pattern of alcohol consumption. Preadolescent animals showed the highest ethanol consumption level. The ADE was only found in adult animals for both alcohol consumption and preference, whereas adolescents showed an ADE only for preference. No effect of sex was detected in any phase of the experiment. [source] Differential Dietary Ethanol Intake and Blood Ethanol Levels in Adolescent and Adult Rats: Effects on Anxiety-Like Behavior and Seizure ThresholdsALCOHOLISM, Issue 8 2008Tiffany A. Wills Background:, Adult rats exhibit increased anxiety-like behavior after exposure to repeated cycles of chronic ethanol and withdrawal. While adolescent rats have differential responses to both acute and chronic ethanol treatments, the potential differences in the effects of repeated withdrawals in this population have yet to be determined. Methods:, Male adult and adolescent rats received three 5-day cycles of either a 4.5% or 7% ethanol diet (ED) separated by two 2-day withdrawal periods. Five hours into the final withdrawal, rats were tested for social interaction (SI) deficits (an index of anxiety-like behavior) and then assessed for seizure thresholds (audiogenic and bicuculline-induced). Ethanol intake was monitored throughout, and blood ethanol concentrations (BEC) were obtained from a separate group of rats. Results:, Adolescent rats have reduced SI during the final withdrawal from either ED and exhibit a greater reduction in SI compared to adult rats when exposed to a 7%ED. Audiogenic seizures were not increased during withdrawal from either ED in adult rats, but adolescent rats that received 7%ED displayed increased seizures. The bicuculline seizure thresholds were decreased in both ages exposed to a 7%ED, but only adolescent rats showed this decreased threshold after 4.5%ED. Ethanol intakes and BECs were higher in adolescent rats compared to similarly treated adults. However, ethanol intakes and BECs were comparable between 4.5%ED-treated adolescent and 7%ED-treated adult rats. Conclusions:, Behavioral results from the 7%ED-treated groups suggested that adolescent rats may be more vulnerable to repeated withdrawals from ethanol than adults; however, differences in ethanol intake and BECs may be at least in part responsible. When ethanol intakes and BECs were similar between 4.5%ED-treated adolescent and 7%ED-treated adult rats, behavioral effects were not different. Importantly, these data illustrated that adolescent rats can exhibit anxiety and reduced seizure thresholds following this repeated withdrawal paradigm. [source] Time Course of Elevated Ethanol Intake in Adolescent Relative to Adult Rats Under Continuous, Voluntary-Access ConditionsALCOHOLISM, Issue 7 2007Courtney S. Vetter Background: Adolescence is a period of elevated alcohol consumption in humans as well as in animal models. Previous studies in our laboratory have shown that adolescent Sprague,Dawley rats consume approximately 2 times more ethanol on a gram per kilogram basis than adult animals in a 2-bottle choice free-access situation. The purpose of the present study was to examine the time course and pattern of elevated ethanol intake during adolescence and the adolescent-to-adult transition, contrast this intake with ontogenetic patterns of food and water intake, and determine whether adolescent access to ethanol elevates voluntary consumption of ethanol in adulthood. Methods: Adolescent [postnatal day (P)27,28] and adult (P69,70) male Sprague,Dawley rats were singly housed with continuous access to both water and 1 of 3 experimental solutions in ball-bearing,containing sipper tubes: unsweetened ethanol (10% v/v), sweetened ethanol (10% v/v+0.1% w/v saccharin), and saccharin alone (0.1% w/v). Results: Ethanol consumption plateaued at approximately 7.5 g/kg/d during the first 2 weeks of measurement (i.e., P28,39) in early adolescence, before declining sharply at approximately P40 to levels that were only modestly elevated compared with adult-typical consumption patterns that were reached by approximately P70. In contrast, intake of food and total calories showed a more gradual decline into adulthood with no distinguishable plateaus in early adolescence. When adolescent-initiated and adult-initiated animals were tested at the same chronological age in adulthood, animals drank similar amounts regardless of the age at which they were first given voluntary access to ethanol. Conclusions: Taken together, these data suggest that the elevated ethanol intake characteristic of early-to-mid adolescence is not simply a function of adolescent-typical hyperphagia or hyperdipsia, but instead may reflect age-related differences in neural substrates contributing to the rewarding or aversive effects of ethanol, as well as possible modulatory influences of ontogenetic differences in sensitivity to novelty or in ethanol pharmacokinetics. Voluntary home cage consumption of ethanol during adolescence, however, was not found to subsequently elevate ethanol drinking in adulthood. [source] Detection of Recent Ethanol Intake With New Markers: Comparison of Fatty Acid Ethyl Esters in Serum and of Ethyl Glucuronide and the Ratio of 5-Hydroxytryptophol to 5-Hydroxyindole Acetic Acid in UrineALCOHOLISM, Issue 5 2005K Borucki Background: At present, recent ethanol consumption can be routinely detected with certainty only by direct measurement of ethanol concentration in blood or urine. Because ethanol is rapidly eliminated from the circulation, however, the time span for this detection is in the range of hours. Several new markers have been proposed to extend the detection interval, but their characteristics have not yet justified their use in routine clinical practice. We therefore investigated three new markers and compared their kinetics and sensitivities: (1) fatty acid ethyl esters (FAEEs) in serum, (2) ethyl glucuronide (EtG) in urine, and (3) the ratio of 5-hydroxytryptophol to 5-hydroxyindole acetic acid (5-HTOL/5-HIAA) in urine. Methods: Seventeen healthy men participated in a drinking experiment. Blood and urine samples were collected twice daily on three consecutive days and once daily on days 4 and 5. Ethanol concentration was determined by gas chromatography, FAEE levels, by gas chromatography with mass spectrometry, EtG concentration, by liquid chromatography-tandem mass spectrometry, and 5-HTOL/5-HIAA ratio, by high-performance liquid chromatography. Results: The peak serum ethanol concentrations of the subjects ranged from 5.4 to 44.7 mmol/liter (mean ± SD, 30.1 ± 9.1 mmol/liter). In the case of the serum ethanol determination, 100% sensitivity was reached only immediately after the end of the drinking experiment, and in the case of FAEE levels and 5-HTOL/5-HIAA ratio, it tested for 6.7 hr after the end of the ethanol intake. Thereafter, these latter parameters declined until 15.3 hr (FAEEs) and 29.4 hr (5-HTOL/5-HIAA), subsequently remaining in a stable range until 78.5 hr without further decrease. In contrast, EtG concentration showed 100% sensitivity until 39.3 hr and thereafter decreased, falling to below the limit of quantification of 0.1 mg/liter at 102.5 hr. Conclusion: After moderate drinking, EtG in the urine proved to be a superior marker of recent ethanol consumption in healthy subjects. This is because EtG is a direct ethanol metabolite, it occurs in the urine only when ethanol has been consumed, and its sensitivity remains at the level of 100% for 39.3 hr. [source] Short and Prolonged Periods of Maternal Separation and Voluntary Ethanol Intake in Male and Female Ethanol-Preferring AA and Ethanol-Avoiding ANA RatsALCOHOLISM, Issue 4 2005Erika Roman Background: Genetic as well as environmental factors can affect the propensity for psychopathology and/or drug dependence. Maternal separation represents an animal experimental model that is useful in studies of effects of early life experiences. The authors have established a protocol for short and prolonged periods of maternal separation to study adult neurochemistry, behavior, and ethanol intake and have previously reported alterations in ethanol intake in Wistar rats and ethanol-preferring rats. The aim of the current study was to more thoroughly study how early life experiences affect an inherited propensity for high and low ethanol intake, respectively, in male and female ethanol-preferring AA (Alko alcohol) and ethanol-avoiding ANA (Alko, Non-Alcohol) rats. Methods: AA and ANA pups were assigned to one of three different rearing conditions: 15 min (MS15) or 360 min (MS360) of daily maternal separation in litters or normal animal facility rearing (AFR) during postnatal days 1 to 21. In adulthood, voluntary ethanol intake was investigated using the two-bottle free choice paradigm. Results: In male ethanol-preferring AA rats, MS15 resulted in a lower intake and fewer high-preferring animals at 8% and 10% ethanol compared with MS360 rats. The male MS360 rats had a higher ethanol intake at 8% and 10% ethanol in comparison with AFR rats. In contrast, the female AA MS15 and MS360 rats had a lower ethanol intake and a lower preference for the 10% ethanol solution compared with the female AA AFR rats. In male and female ANA rats, no major separation-induced effects were found. Conclusions: The current results show that genetic inheritance can be affected by environmental manipulations in AA rats with an inherent high ethanol intake. The findings in female ethanol-preferring AA rats give further evidence of a differential outcome of maternal separation in male and female rats, as previously shown. [source] Helplessness in the Tail Suspension Test Is Associated with an Increase in Ethanol Intake and Its Rewarding Effect in Female MiceALCOHOLISM, Issue 3 2005Yann Pelloux Background: Depression is frequently observed in drug abusers. However, depression may be a primary factor of predisposition to drug abuse or a consequence of drug abuse. The aim of this study was to analyze the influence of a preexisting depressive-like state/helplessness on subsequent alcohol responsiveness in mice. Methods: Male and female CD1 mice were selected according to their immobility time in the tail suspension test, and only mice with "high immobility" and "low immobility" time were retained. Using a two-bottle free-choice paradigm, these mice were given continuous access to tap water or solutions of ethanol (3,20% v/v), quinine (12.5,50 mg/liter), or sucrose (1,4% w/v). In female mice, rewarding and aversive effects of ethanol (1.5 and 3 g/kg, intraperitoneally) were also investigated using the conditioned place preference and the conditioned taste aversion paradigms. Results: Female mice were more immobile and drank more ethanol than male mice. No striking sex difference was observed in quinine consumption. Sucrose intake was higher in female than in male mice, whatever the solution concentration. At the 4% concentrated solution, a sucrose-induced increase in daily fluid intake was observed only in female mice. Female mice with high immobility time (HI) consumed more ethanol at the highest concentration than female mice with low immobility time (LI), whereas no difference was observed between HI and LI male mice. Moreover, whereas LI female mice failed to express place conditioning induced by the 3-g/kg dose of ethanol, HI female mice were strongly responsive to the rewarding effect of this high ethanol dose. Ethanol dose-dependently induced a conditioned taste aversion with a similar magnitude in both LI and HI female mice. Conclusions: The findings indicate that female CD1 mice tend to drink greater amounts of ethanol or sucrose solutions than male CD1 mice, suggesting that female mice may be a better model of excessive alcohol intake. Furthermore, no relationship was found between immobility scores and ethanol consumption in male mice. On the contrary, within female mice, HI mice consumed higher amounts of ethanol than LI mice probably because they experienced greater rewarding effects of ethanol. The present results support the hypothesis that depressive-like responses may predispose to ethanol abuse in female mice. [source] Effect of Neuropeptide Y (NPY) on Oral Ethanol Intake in Wistar, Alcohol-Preferring (P), and -Nonpreferring (NP) RatsALCOHOLISM, Issue 3 2001N.E. Badia-Elder Background: Neuropeptide Y (NPY) deficient mice consume more ethanol than controls, whereas NPY over-expressing mice consume less ethanol than controls. Thus, ethanol drinking may be inversely associated with NPY activity. To determine whether exogenously administered NPY would alter ethanol intake, two experiments were conducted. Methods: A within-subject design was used with intracerebroventricular (ICV) administration of NPY or artificial cerebral spinal fluid (aCSF) into the lateral ventricles. Infusions were separated by 2 to 7 days. In experiment 1, male Wistar rats (n= 10) were tested for the effects of NPY on an intake of 5% sucrose or 8% (w/v) ethanol during daily 2-hr testing periods with food and water available at all other times. In experiment 2, male alcohol-preferring (P) and alcohol-nonpreferring (NP) rats (n= 8/line) were tested for the effects of NPY on 8% (w/v) ethanol intake. Results: In experiment 1, NPY (5, 10, 20 ,g) significantly increased sucrose intake relative to aCSF baseline in Wistar rats, a finding consistent with previous observations of the orexigenic effects of the peptide. However, NPY (10 ,g) did not alter ethanol intake in Wistar rats. In experiment 2, NPY (5 and 10 ,g) significantly decreased ethanol intake in P rats, but not in NP rats. Conclusion: The reduction in ethanol intake seen with the P rats is consistent with the postulated negative relationship between NPY activity and ethanol intake. The lack of effect of NPY on ethanol intake in Wistar and NP rats may be related to the lower baseline levels of ethanol intake in these rats or to differential central nervous system basal NPY activity or sensitivity to the peptide. [source] Role of Wake-Promoting Basal Forebrain and Adenosinergic Mechanisms in Sleep-Promoting Effects of EthanolALCOHOLISM, Issue 6 2010Mahesh M. Thakkar Background:, Ethanol intake has significant impact on sleep. However, the cellular substrates responsible for sleep promotion following ethanol intake are unknown. The purine nucleoside, adenosine, is responsible for mediating many neuronal and behavioral responses to ethanol. Studies performed in cell cultures suggest that ethanol inhibits equilibrative nucleoside transporter 1 to block the reuptake of adenosine resulting in increased extracellular adenosine. Adenosine also has a pivotal role in sleep regulation. Adenosine acts via A1 receptor to inhibit the wake-promoting neurons of the basal forebrain (BF) resulting in the promotion of sleep. Is ethanol-induced sleep associated with the inhibition of the BF wake-promoting neurons? Do adenosinergic mechanisms in the BF have a role in sleep-promoting effects of ethanol? Methods:, To address these questions, we performed 3 experiments in Sprague,Dawley rats. First, we verified the effect of ethanol on sleep promotion. Second, we evaluated the effect of ethanol on c-Fos expression (a marker of neuronal activation) in the BF wake-promoting neurons and third we monitored the effects of A1 receptor blockade in the BF on ethanol-induced sleep. Results:, Significant increase in non-rapid eye movement (NREM) sleep with a concomitant decrease in wakefulness was observed during the first 12 hours postethanol. REM sleep remained unaffected. Ethanol administration caused a significant decrease in the number of BF wake-promoting neurons with c-Fos immunoreactivity. Bilateral microinjections of a selective A1R receptor antagonist 8-cyclopentyl-1, 3-dipropylxanthine into the BF significantly attenuated sleep-promoting effects of ethanol. Conclusion:, These results suggest that the inhibition of BF wake-promoting neurons by adenosinergic mechanism may be responsible for the sleep promoting effects of ethanol. We believe our study is the first to investigate the cellular mechanisms responsible for the somnogenic effects of ethanol. [source] CB1 Receptor Blockade Decreases Ethanol Intake and Associated Neurochemical Changes in Fawn-Hooded RatsALCOHOLISM, Issue 1 2010Teresa Femenía Background:, This study was undertaken to identify the neurochemical changes underlying the attenuation of voluntary ethanol intake induced by the cannabinoid CB1 receptor antagonist AM251 in fawn-hooded rats. Methods:, Rats were exposed to the 2-bottle-choice paradigm (ethanol 10% v/v or water) for 15 days. After this period, rats received AM251 (3 to 6 mg/kg, i.p.) or vehicle. Results:, Voluntary ethanol intake decreased (30%) with the administration of incremental dosages of AM251 (3 mg/kg, 5 days and 6 mg/kg, 5 days) in rats with acquired high preferring ethanol consumption (>3.5 g of ethanol/kg/d). Ethanol intake significantly decreased proopiomelanocortin expression in the arcuate nucleus (38.31%) and ,-opioid-DAMGO-stimulated [35S]-GTP, binding in the caudate-putamen (40%), nucleus accumbens core (AccC) (32.87%), and shell (AccS) (34.21%). Moreover, ethanol intake increased tyrosine hydroxylase (TH) gene expression in the substantia nigra (24%) and ventral tegmental area (23%) and corticotrophin-releasing gene expression in the paraventricular hypothalamic nucleus (41.6%). The reduction of ethanol intake induced by AM251 was associated with blockade or significant reduction of the changes produced by ethanol in the expression of these genes in key regions related to drug dependence. Interestingly, treatment with AM251 reduced (20%) TH gene expression in rats drinking only water. In this respect, the action of AM251 in reducing TH gene expression may not be specific. Conclusion:, Taken together, these results revealed that blockade of cannabinoid CB1 receptors (CB1r) decreased voluntary ethanol intake in ethanol-habituated rats by normalizing the neurochemical alterations induced by ethanol. [source] Patterns of Ethanol Intake in Preadolescent, Adolescent, and Adult Wistar Rats Under Acquisition, Maintenance, and Relapse-Like ConditionsALCOHOLISM, Issue 4 2009David García-Burgos Background:, Animal behavioral models of voluntary ethanol consumption represent a valuable tool to investigate the relationship between age and propensity to consume alcohol using an experimental methodology. Although adolescence has been considered as a critical age, few are the studies that consider the preadolescence age. This study examines the ethanol consumption/preference and the propensity to show an alcohol deprivation effect (ADE) after a short voluntary ethanol exposure from a developmental perspective. Methods:, Three groups of heterogeneous Wistar rats of both sexes with ad libitum food and water were exposed for 10 days to 3 ethanol solutions at 3 different ontogenetic periods: preadolescence (PN19), adolescence (PN28), and adulthood (PN90). Ethanol intake (including circadian rhythm), ethanol preference, water and food consumption, and ADE were measured. Results:, During the exposure, the 3 groups differed in their ethanol intake; the greatest amount of alcohol (g/kg) was consumed by the preadolescent rats while the adolescents showed a progressive decrease in alcohol consumption as they approached the lowest adult levels by the end of the assessed period. The pattern of ethanol consumption was not fully explained in terms of hyperphagia and/or hyperdipsia at early ages, and showed a wholly circadian rhythm in adolescent rats. After an abstinence period of 7 days, adult rats showed an ADE measured both as an increment in ethanol consumption and preference, whereas adolescent rats only showed an increment in ethanol preference. Preadolescent rats decreased their consumption and their preference remained unchanged. Conclusions:, In summary, using a short period of ethanol exposure and a brief deprivation period the results revealed a direct relationship between chronological age and propensity to consume alcohol, being the adolescence a transition period from the infant to the adult pattern of alcohol consumption. Preadolescent animals showed the highest ethanol consumption level. The ADE was only found in adult animals for both alcohol consumption and preference, whereas adolescents showed an ADE only for preference. No effect of sex was detected in any phase of the experiment. [source] Sensitization, Duration, and Pharmacological Blockade of Anxiety-Like Behavior Following Repeated Ethanol Withdrawal in Adolescent and Adult RatsALCOHOLISM, Issue 3 2009Tiffany A. Wills Background:, Repeated ethanol withdrawal sensitizes anxiety-like behavior in adult rats and causes anxiety-like behavior and decreased seizure thresholds in adolescent rats. Current experiments determined if adolescent rats exhibit sensitized anxiety-like behavior, the duration of this effect, if drug pretreatments blocked these effects, and if these effects differed from those seen in adults. Methods:, Male adolescent rats received three 5-day cycles of 2.5% ethanol diet (ED) separated by two 2-day withdrawal periods, continuous 15 days of 2.5%ED, or a single 5-day cycle of 2.5%ED. Male adult rats received three 5-day cycles of either 2.5% or 3.5%ED. These groups were tested 5 hours into the final withdrawal for social interaction (SI) deficits (an index of anxiety-like behavior). Ethanol intake was monitored throughout and blood concentrations were obtained from separate groups of rats. Additionally, adolescent rats were tested for SI 1, 2, 7, 14, and 18 days and adults 1 and 2 days after the final withdrawal. Some adolescent rats were also pretreated with the CRF1 antagonist CP-154,526, the 5-HT1A agonist buspirone, or the benzodiazepine receptor antagonist flumazenil during the first 2 withdrawals. Results:, SI was reduced in adolescent rats following repeated withdrawals of 2.5%ED while neither a continuous or single cycle ED exposure caused this effect. Adult rats also had reduced SI following repeated withdrawals from both 2.5% and 3.5%ED. This effect was present up to 1 week following the final withdrawal in adolescents but returned to baseline by 1 day in adults. CP-154,526, buspirone, or flumazenil prevented this reduction in SI in adolescent rats. Conclusions:, Adolescent rats exhibit sensitized anxiety-like behavior following repeated withdrawals at ED concentrations similar to those used in adults. However, this effect is longer lasting in adolescent rats. Drugs modulating CRF, 5-HT, or GABA systems during initial withdrawals prevent the development of anxiety-like behavior otherwise manifest during a final withdrawal in adolescent rats. [source] Differential Dietary Ethanol Intake and Blood Ethanol Levels in Adolescent and Adult Rats: Effects on Anxiety-Like Behavior and Seizure ThresholdsALCOHOLISM, Issue 8 2008Tiffany A. Wills Background:, Adult rats exhibit increased anxiety-like behavior after exposure to repeated cycles of chronic ethanol and withdrawal. While adolescent rats have differential responses to both acute and chronic ethanol treatments, the potential differences in the effects of repeated withdrawals in this population have yet to be determined. Methods:, Male adult and adolescent rats received three 5-day cycles of either a 4.5% or 7% ethanol diet (ED) separated by two 2-day withdrawal periods. Five hours into the final withdrawal, rats were tested for social interaction (SI) deficits (an index of anxiety-like behavior) and then assessed for seizure thresholds (audiogenic and bicuculline-induced). Ethanol intake was monitored throughout, and blood ethanol concentrations (BEC) were obtained from a separate group of rats. Results:, Adolescent rats have reduced SI during the final withdrawal from either ED and exhibit a greater reduction in SI compared to adult rats when exposed to a 7%ED. Audiogenic seizures were not increased during withdrawal from either ED in adult rats, but adolescent rats that received 7%ED displayed increased seizures. The bicuculline seizure thresholds were decreased in both ages exposed to a 7%ED, but only adolescent rats showed this decreased threshold after 4.5%ED. Ethanol intakes and BECs were higher in adolescent rats compared to similarly treated adults. However, ethanol intakes and BECs were comparable between 4.5%ED-treated adolescent and 7%ED-treated adult rats. Conclusions:, Behavioral results from the 7%ED-treated groups suggested that adolescent rats may be more vulnerable to repeated withdrawals from ethanol than adults; however, differences in ethanol intake and BECs may be at least in part responsible. When ethanol intakes and BECs were similar between 4.5%ED-treated adolescent and 7%ED-treated adult rats, behavioral effects were not different. Importantly, these data illustrated that adolescent rats can exhibit anxiety and reduced seizure thresholds following this repeated withdrawal paradigm. [source] Effects of Neuropeptide Y on Appetitive and Consummatory Behaviors Associated With Alcohol Drinking in Wistar Rats With a History of Ethanol ExposureALCOHOLISM, Issue 4 2005Annika Thorsell Background: Neuropeptide Y (NPY) reduces ethanol intake under free access conditions in Wistar rats with a history of prolonged ethanol vapor exposure. The current study was designed to determine whether NPY differentially alters ethanol-associated appetitive behavior (i.e., lever pressing) or ethanol consumption in Wistar rats with a history of ethanol vapor exposure. Methods: Wistar rats were first trained to self-administer 10% ethanol in a paradigm that provided 25 min of free access to 10% ethanol after completing a 20,lever press response requirement (i.e., an RR20 schedule). After stable level lever pressing was established, operant sessions were suspended during a 9-week period of ethanol vapor exposure. Self-administration sessions were then reinstituted, and a fixed time (FT) schedule of 10% ethanol access was used to assess the effects of ethanol exposure and NPY on lever pressing and drinking behavior. Under the FT schedule, the maximum number of lever presses emitted within 10 min was assessed before providing access to 10% ethanol. Results: Ethanol vapor exposure did not alter patterns of lever pressing under the RR20 schedule, but lever presses emitted under the FT schedule were reduced after ethanol vapor exposure. Ethanol intake was significantly increased after ethanol vapor exposure. NPY significantly reduced ethanol intake but did not significantly reduce lever pressing under the FT schedule. Conclusions: Taken together, these data suggest that chronic ethanol exposure increases ethanol intake without clearly enhancing its reinforcing value. Furthermore, NPY has a greater impact on the consummatory factors mediating ethanol intake than appetitive factors mediating ethanol seeking. [source] Gender-specific vascular effects elicited by chronic ethanol consumption in rats: a role for inducible nitric oxide synthaseBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2008C R Tirapelli Background and purpose: Epidemiological data suggest that the risk of ethanol-associated cardiovascular disease is greater in men than in women. This study investigates the mechanisms underlying gender-specific vascular effects elicited by chronic ethanol consumption in rats. Experimental approach: Vascular reactivity experiments using standard muscle bath procedures were performed on isolated thoracic aortae from rats. mRNA and protein for inducible NO synthase (iNOS) and for endothelial NOS (eNOS) was assessed by RT-PCR or western blotting, respectively. Key results: In male rats, chronic ethanol consumption enhanced phenylephrine-induced contraction in both endothelium-intact and denuded aortic rings. However, in female rats, chronic ethanol consumption enhanced phenylephrine-induced contraction only in endothelium denuded aortic rings. After pre-incubation of endothelium-intact rings with L -NAME, both male and female ethanol-treated rats showed larger phenylephrine-induced contractions in aortic rings, compared to the control group. Acetylcholine-induced relaxation was not affected by ethanol consumption. The effects of ethanol on responses to phenylephrine were similar in ovariectomized (OVX) and intact (non-OVX) female rats. In the presence of aminoguanidine, but not 7-nitroindazole, the contractions to phenylephrine in rings from ethanol-treated female rats were greater than that found in control tissues in the presence of the inhibitors. mRNA levels for eNOS and iNOS were not altered by ethanol consumption. Ethanol intake reduced eNOS protein levels and increased iNOS protein levels in aorta from female rats. Conclusions and implications: Gender differences in the vascular effects elicited by chronic ethanol consumption were not related to ovarian hormones but seemed to involve the upregulation of iNOS. British Journal of Pharmacology (2008) 153, 468,479; doi:10.1038/sj.bjp.0707589; published online 26 November 2007 [source] Differential Dietary Ethanol Intake and Blood Ethanol Levels in Adolescent and Adult Rats: Effects on Anxiety-Like Behavior and Seizure ThresholdsALCOHOLISM, Issue 8 2008Tiffany A. Wills Background:, Adult rats exhibit increased anxiety-like behavior after exposure to repeated cycles of chronic ethanol and withdrawal. While adolescent rats have differential responses to both acute and chronic ethanol treatments, the potential differences in the effects of repeated withdrawals in this population have yet to be determined. Methods:, Male adult and adolescent rats received three 5-day cycles of either a 4.5% or 7% ethanol diet (ED) separated by two 2-day withdrawal periods. Five hours into the final withdrawal, rats were tested for social interaction (SI) deficits (an index of anxiety-like behavior) and then assessed for seizure thresholds (audiogenic and bicuculline-induced). Ethanol intake was monitored throughout, and blood ethanol concentrations (BEC) were obtained from a separate group of rats. Results:, Adolescent rats have reduced SI during the final withdrawal from either ED and exhibit a greater reduction in SI compared to adult rats when exposed to a 7%ED. Audiogenic seizures were not increased during withdrawal from either ED in adult rats, but adolescent rats that received 7%ED displayed increased seizures. The bicuculline seizure thresholds were decreased in both ages exposed to a 7%ED, but only adolescent rats showed this decreased threshold after 4.5%ED. Ethanol intakes and BECs were higher in adolescent rats compared to similarly treated adults. However, ethanol intakes and BECs were comparable between 4.5%ED-treated adolescent and 7%ED-treated adult rats. Conclusions:, Behavioral results from the 7%ED-treated groups suggested that adolescent rats may be more vulnerable to repeated withdrawals from ethanol than adults; however, differences in ethanol intake and BECs may be at least in part responsible. When ethanol intakes and BECs were similar between 4.5%ED-treated adolescent and 7%ED-treated adult rats, behavioral effects were not different. Importantly, these data illustrated that adolescent rats can exhibit anxiety and reduced seizure thresholds following this repeated withdrawal paradigm. [source] Using drinking in the dark to model prenatal binge-like exposure to ethanol in C57BL/6J miceDEVELOPMENTAL PSYCHOBIOLOGY, Issue 6 2008Stephen L. Boehm II Abstract Animal models of prenatal ethanol exposure are necessary to more fully understand the effects of ethanol on the developing embryo/fetus. However, most models employ procedures that may produce additional maternal stress beyond that produced by ethanol alone. We employed a daily limited-access ethanol intake model called Drinking in the Dark (DID) to assess the effects of voluntary maternal binge-like ethanol intake on the developing mouse. Evidence suggests that binge exposure may be particularly harmful to the embryo/fetus, perhaps due to the relatively higher blood ethanol concentrations achieved. Pregnant females had mean daily ethanol intakes ranging from 4.2 to 6.4 g/kg ethanol over gestation, producing blood ethanol concentrations ranging from 115 to 182 mg/dL. This level of ethanol intake produced behavioral alterations among adolescent offspring that disappeared by adulthood, including altered sensitivity to ethanol's hypnotic actions. The DID model may provide a useful tool for studying the effects of prenatal ethanol exposure in mice. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 566,578, 2008. [source] Should symptom frequency be factored into scalar measures of alcohol use disorder severity?ADDICTION, Issue 9 2010Deborah A. Dawson ABSTRACT Aims To evaluate whether weighting counts of alcohol use disorder (AUD) criteria or symptoms by their frequency of occurrence improves their association with correlates of AUD. Design and participants Data were collected in personal interviews with a representative sample of US adults interviewed in 1991,92. Analyses were conducted among past-year drinkers (12+ drinks, n = 18 352) and individuals with past-year DSM-IV AUD (n = 2770). Measurements Thirty-one symptom item indicators, whose frequency of occurrence was measured in eight categories, were used to create unweighted and frequency-weighted counts of DSM-IV past-year AUD symptoms and criteria. Correlates included density of familial alcoholism and past-year volume of ethanol intake, frequency of intoxication and utilization of alcohol treatment. Findings Although the AUD correlates were associated strongly and positively with the frequency of AUD symptom occurrence, weighting for symptom frequency did not strengthen their association consistently with AUD severity scores. Improved performance of the weighted scores was observed primarily among AUD correlates linked closely with the frequency of heavy drinking and among individuals with AUD. Criterion counts were correlated nearly as strongly as symptom counts with the AUD correlates. Conclusions Frequency weighting may add somewhat to the validity of AUD severity measures, especially those that are intended for use among individuals with AUD, e.g. in clinical settings. For studying the etiology and course of AUD in the general population, an equally effective and less time-consuming alternative to obtaining symptom frequency may be the use of unweighted criterion counts accompanied by independent measures of frequency of heavy drinking. [source] CLINICAL STUDY: FULL ARTICLE: Immunomodulating properties of gamma-hydroxybutyrate (GHB), flunitrazepam and ethanol in ,club drugs' usersADDICTION BIOLOGY, Issue 3 2010Simona Pichini ABSTRACT Despite the increasing concern about gamma-hydroxybutyrate (GHB) toxicity in users, no studies have addressed GHB and other club drugs effects on the immune system under controlled administration. Lymphocyte subsets and functional responsiveness of lymphocytes to mitogenic stimulation were measured in 10 healthy male recreational users of GHB who participated in five experimental sessions within the framework of a clinical trial. The study was randomized, double blind, double dummy and cross-over. Drug conditions were: a single oral dose of GHB (40 mg/kg or 60 mg/kg), ethanol (0.7 g/kg), flunitrazepam (1.25 mg) and placebo. Acute GHB produced a time-dependent immune impairment in the first 4 hours after drug administration associated with an increase in cortisol secretion. Although total leukocyte count remained unchanged, there was a significant decrease in the CD4 T/CD8 T-cell ratio, as well as in the percentage of mature T lymphocytes, probably because of a decrease in both the percentage and absolute number of T helper cells. A significant decrease was also observed in natural killer cells and in functional responsiveness of lymphocytes to mitogenic stimulation. Flunitrazepam administration did not produce any change in the immune system, while ethanol intake produced a decrease in B lymphocytes and in lymphocyte proliferative response to mitogens. These results provide the first evidence that GHB intake under a controlled environmental setting impairs the immunological status and confirms the alterations in the immune function caused by ethanol. [source] CLINICAL STUDY/BIOMARKER: Phosphatidylethanol: normalization during detoxification, gender aspects and correlation with other biomarkers and self-reportsADDICTION BIOLOGY, Issue 1 2010Friedrich Martin Wurst ABSTRACT Phosphatidylethanol (PEth) is a direct ethanol metabolite, and has recently attracted attention as biomarker of ethanol intake. The aims of the current study are: (1) to characterize the normalization time of PEth in larger samples than previously conducted; (2) to elucidate potential gender differences; and (3) to report the correlation of PEth with other biomarkers and self-reported alcohol consumption. Fifty-seven alcohol-dependent patients (ICD 10 F 10.25; 9 females, 48 males) entering medical detoxification at three study sites were enrolled. The study sample was comprised of 48 males and 9 females, with mean age 43.5. Mean gamma glutamyl transpeptidase (GGT) was 209.61 U/l, average mean corpuscular volume (MCV) was 97.35 fl, mean carbohydrate deficient transferrin (%CDT) was 8.68, and mean total ethanol intake in the last 7 days was 1653 g. PEth was measured in heparinized whole blood with a high-pressure liquid chromatography method, while GGT, MCV and %CDT were measured using routine methods. PEth levels at day 1 of detoxification ranged between 0.63 and 26.95 µmol/l (6.22 mean, 4.70 median, SD 4.97). There were no false negatives at day 1. Sensitivities for the other biomarkers were 40.4% for MCV, 73.1% for GGT and 69.2% for %CDT, respectively. No gender differences were found for PEth levels at any time point. Our data suggest that PEth is (1) a suitable intermediate term marker of ethanol intake in both sexes; and (2) sensitivity is extraordinary high in alcohol dependent patients. The results add further evidence to the data that suggest that PEth has potential as a candidate for a sensitive and specific biomarker, which reflects longer-lasting intake of higher amounts of alcohol and seemingly has the above mentioned certain advantages over traditional biomarkers. [source] PRECLINICAL STUDY: Effect of concurrent saccharin intake on ethanol consumption by high-alcohol-drinking (UChB) ratsADDICTION BIOLOGY, Issue 3 2009Lutske Tampier ABSTRACT This study examined the effect of concurrent presentation of a highly palatable saccharin solution on ethanol consumption during the acquisition or maintenance of ethanol drinking by high-alcohol-drinking (UChB) rats. Rats were exposed to ethanol (10% v/v) and water under a home cage, two-bottle, free-choice regimen with unlimited access for 24 hours/day. After 7 days (acquisition) of ethanol exposure, a third bottle containing saccharin (0.2% w/v) was concomitantly offered for an additional seven consecutive days, and the same process was repeated after 3 months (maintenance) of ethanol exposure. We found that concurrent saccharin intake significantly reduced ethanol intake by UChB rats after 7 days of ethanol exposure indicating that preference for sweet taste tends to override the preference for ethanol. However, the concurrent saccharin presentation to rats after 3 months of stable ethanol consumption did not reduce ethanol intake, whereas their saccharin consumption reached polydipsic-like values. These results support the notion that in UChB rats, a time-dependent sensitization to the rewarding effects of ethanol is developed that may account for the increases in ethanol volition seen following chronic ethanol intake. [source] PRECLINICAL STUDY: Effects of concurrent access to multiple ethanol concentrations and repeated deprivations on alcohol intake of high-alcohol-drinking (HAD) ratsADDICTION BIOLOGY, Issue 2 2009Zachary A. Rodd ABSTRACT High-alcohol-drinking rats, given access to 10% ethanol, expressed an alcohol deprivation effect (ADE) only after multiple deprivations. In alcohol-preferring (P) rats, concurrent access to multiple ethanol concentrations combined with repeated cycles of EtOH access and deprivation produced excessive ethanol drinking. The current study was undertaken to examine the effects of repeated alcohol deprivations with concurrent access to multiple concentrations of ethanol on ethanol intake of HAD replicate lines of rats. HAD-1 and HAD-2 rats received access to 10, 20 and 30% (v/v) ethanol for 6 weeks. Rats from each replicate line were assigned to: (1) a non-deprived group; (2) a group initially deprived of ethanol for 2 weeks; or (3) a group initially deprived for 8 weeks. Following the restoration of the ethanol solutions, cycle of 2 weeks of ethanol exposure and 2 weeks of alcohol deprivation was repeated three times for a total of four deprivations. Following the initial ethanol deprivation period, deprived groups significantly increased ethanol intakes during the initial 24-hour re-exposure period. Multiple deprivations increased ethanol intakes, shifted preference to higher ethanol concentrations and prolonged the duration of the elevated ethanol intakes for up to 5 days. In addition, repeated deprivations increased ethanol intake in the first 2-hour re-exposure period as high as 5,7 g/kg (which are equivalent to amounts consumed in 24 hours by HAD rats), and produced blood ethanol levels in excess of 150 mg%. The results indicate that HAD rats exhibit ,loss-of-control' of alcohol drinking with repeated deprivations when multiple ethanol concentrations are available. [source] BIOMARKER: Phosphatidylethanol as a sensitive and specific biomarker,comparison with gamma-glutamyl transpeptidase, mean corpuscular volume and carbohydrate-deficient transferrinADDICTION BIOLOGY, Issue 1 2007Susanne Hartmann ABSTRACT Phosphatidylethanol (PEth), a direct ethanol metabolite, is detectable in blood for more than 2 weeks after sustained ethanol intake. Our aim was to assess the usefulness of PEth [comparing sensitivity, specificity and the area under the curve (AUC)] as compared with carbohydrate-deficient transferrin (CDT), gamma-glutamyl transpeptidase (GGT) and mean corpuscular volume (MCV), calculating the results from sober patients against those from alcohol-dependent patients during withdrawal. Fifty-six alcohol-dependent patients (ICD-10 F 10.25) in detoxification, age 43 years, GGT 81 U/l, MCV 96.4 fl, %CDT 4.2, 1400 g ethanol intake in the last 7 days (median), were included in the study. Over the time of 1 year, 52 samples from 35 sober forensic psychiatric addicted in-patients [age 34 years, GGT 16 U/l, MCV 91 fl, CDT 0.5 (median)] in a closed ward were drawn and used for comparison . PEth was measured in heparinized whole blood with a high-performance liquid chromatography method. GGT, MCV and %CDT were measured using routine methods. A receiver operating characteristic curve analysis was carried out, with ,current drinking status' (sober/drinking) as the state variable and PEth, MCV, GGT and CDT as test variables. The resulting AUC was 0.974 (P < 0.0001, confidence interval 0.932,1.016) for PEth. At a cut-off of 0.36 µmol/l, the sensitivity was 94.5% and specificity 100%. The AUC for CDT, GGT and MCV were 0.931, 0.894 and 0.883, respectively. A significant Spearman's rank correlation was found between PEth and GGT (r = 0.739), CDT (r = 0.643), MVC (r = 0.639) and grams of ethanol consumed in the last 7 days (r = 0.802). Our data suggest that PEth has potential to be a sensitive and specific biomarker, having been found in previous studies to indicate longer lasting intake of higher amounts of alcohol. [source] REVIEW: The alcohol-preferring P rat and animal models of excessive alcohol drinkingADDICTION BIOLOGY, Issue 3-4 2006Richard L. Bell ABSTRACT The alcohol-preferring, P, rat was developed by selective breeding to study ethanol drinking behavior and its consequences. Characterization of this line indicates the P rat meets all of the criteria put forth for a valid animal model of alcoholism, and displays, relative to their alcohol-non-preferring, NP, counterparts, a number of phenotypic traits associated with alcohol abuse and alcoholism. Behaviorally, compared with NP rats, P rats are less sensitive to the sedative and aversive effects of ethanol and more sensitive to the stimulatory effects of ethanol. Neurochemically, research with the P line indicates the endogenous dopaminergic, serotonergic, GABAergic, opiodergic, and peptidergic systems may be involved in a predisposition for alcohol abuse and alcoholism. Paralleling the clinical literature, genetically selected P rats display levels of ethanol intake during adolescence comparable to that seen during adulthood. Binge drinking has been associated with an increased risk for health and other problems associated with ethanol abuse. A model of binge-like drinking during the dark cycle indicates that P rats will consume 6 g/kg/day of ethanol in as little as three 1-hour access periods/day, which approximates the 24-hour intake of P rats with free-choice access to a single concentration of ethanol. The alcohol deprivation effect (ADE) is a transient increase in ethanol intake above baseline values upon re-exposure to ethanol access after an extended period of deprivation. The ADE has been proposed to be an animal model of relapse behavior, with the adult P rat displaying a robust ADE after prolonged abstinence. Overall, these findings indicate that the P rat can be effectively used in models assessing alcohol-preference, a genetic predisposition for alcohol abuse and/or alcoholism, and excessive drinking using protocols of binge-like or relapse-like drinking. [source] Reduced ethanol response in the alcohol-preferring RHA rats and neuropeptide mRNAs in relevant structuresEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2006Marc Guitart-Masip Abstract Roman rat strains, genetically selected for high (RHA) or low (RLA) active avoidance acquisition in the two-way shuttle box, differ in dopaminergic activity. These two strains appear to be a valid laboratory model of divergent sensation/novelty and substance-seeking profiles. RHA rats show higher ethanol intake and preference than do RLA rats, and it was suggested that RHA rats are more tolerant than RLA to the effects of alcohol. In the hole-board test, we found that the non-alcohol-preferring RLA rats showed enhanced responsiveness to the stimulatory effects of intraperitoneal administration of 0.25 g/kg ethanol when compared with RHA rats. In situ hybridization analysis showed higher levels of preprodynorphin in the accumbens shell and higher levels of preproenkephalin in the cingulate cortex in RHA rats. RLA rats showed higher levels of enkephalin gene transcripts in restricted areas of the dorsal striatum. Finally, differences in cholecystokinin gene transcript, suggestive of a different arrangement of certain interneurons, were found in different cortical areas. The differences in peptide gene expression found between the two strains might reflect the differences in alcohol preference and sensitivity. RHA rats may have more predictive value than other rodent alcoholism models, as high initial tolerance to ethanol is a risk factor for alcoholism in humans. [source] Perception of sweet taste is important for voluntary alcohol consumption in miceGENES, BRAIN AND BEHAVIOR, Issue 1 2008Y. A. Blednov To directly evaluate the association between taste perception and alcohol intake, we used three different mutant mice, each lacking a gene expressed in taste buds and critical to taste transduction: ,-gustducin (Gnat3), Tas1r3 or Trpm5. Null mutant mice lacking any of these three genes showed lower preference score for alcohol and consumed less alcohol in a two-bottle choice test, as compared with wild-type littermates. These null mice also showed lower preference score for saccharin solutions than did wild-type littermates. In contrast, avoidance of quinine solutions was less in Gnat3 or Trpm5 knockout mice than in wild-type mice, whereas Tas1r3 null mice were not different from wild type in their response to quinine solutions. There were no differences in null vs. wild-type mice in their consumption of sodium chloride solutions. To determine the cause for reduction of ethanol intake, we studied other ethanol-induced behaviors known to be related to alcohol consumption. There were no differences between null and wild-type mice in ethanol-induced loss of righting reflex, severity of acute ethanol withdrawal or conditioned place preference for ethanol. Weaker conditioned taste aversion (CTA) to alcohol in null mice may have been caused by weaker rewarding value of the conditioned stimulus (saccharin). When saccharin was replaced by sodium chloride, no differences in CTA to alcohol between knockout and wild-type mice were seen. Thus, deletion of any one of three different genes involved in detection of sweet taste leads to a substantial reduction of alcohol intake without any changes in pharmacological actions of ethanol. [source] | ||||||||||||||||