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Alcohol Administration (alcohol + administration)

Distribution by Scientific Domains

Medical Sciences	96%

Selected Abstracts

Intravenous Ethanol Infusions Can Mimic the Time Course of Breath Alcohol Concentrations Following Oral Alcohol Administration in Healthy Volunteers

ALCOHOLISM, Issue 5 2009
Vijay A. Ramchandani
Background:, Our previous studies have used intravenous (IV) clamping methods to demonstrate that family history positive (FHP) subjects exhibit a greater initial response to alcohol than family history negative (FHN) subjects. These results differ from other studies of family history of alcoholism (FHA) influences, most of which have used an oral alcohol challenge, suggesting that the route of administration may influence both the response to alcohol and FHA-related differences in response. To examine this possibility, one approach would be to directly compare responses following oral and IV alcohol administration in the same subjects. There is, however, a 3- to 4-fold variance, between- and within-subjects, in the breath alcohol concentrations (BrACs) following oral alcohol administration. Thus, our objective was to characterize the between-subject variability in the time course of BrACs following oral alcohol administration in healthy volunteers and to develop an IV infusion method to mimic the BrAC-time course attained following oral alcohol in the same subject. Methods:, This was a 2-session study in young adult, healthy, nondependent drinkers. In the first session, subjects ingested an oral dose of alcohol, based on total body water, to achieve a target peak BrAC of 80 mg%. In the second session, subjects received an IV infusion of ethanol designed to achieve the same BrAC time course as that achieved in the first session. The individualized infusion-rate profile was precomputed using a physiologically-based pharmacokinetic (PBPK) model for alcohol with model parameters adjusted to the individual's physiology. The peak BrACs (Cmax), times of peak BrAC (Tmax), and the areas under the BrAC vs. time curve (AUC) were compared between sessions to assess how closely the BrAC exposure during the IV infusion session mimicked the exposure following oral alcohol. Results:, The time course of BrACs following oral alcohol administration showed a high degree of between-subject variability. Mean Cmax, Tmax, and AUC did not differ by gender, indicating that calculation of oral doses based on total body water results in comparable BrAC-time courses, on average, for females and males. The IV infusion driven BrAC-time profiles demonstrated good fidelity to the BrAC-time curves resulting from oral alcohol: the mean %difference in Cmax and AUC were both 11%, while the mean %difference for Tmax was 27%. This degree of variability is less than half that seen across individuals following oral alcohol administration, which was substantial [coefficient of variation (%CV) ranging from 22 to 52%]. Conclusions:, Despite the use of standardized doses and controlled experimental conditions, there was substantial between-subject variability in the BrAC time course following oral administration of alcohol. The PBPK-model-based infusion method can mimic the BrACs attained with oral alcohol for individual subjects. This method provides a platform to evaluate effects attributable to the route of administration on the response to alcohol, as well as the influence of determinants such as family history of alcoholism on the alcohol response. [source]

When What You See Isn't What You Get: Alcohol Cues, Alcohol Administration, Prediction Error, and Human Striatal Dopamine

ALCOHOLISM, Issue 1 2009
Karmen K. Yoder
Background:, The mesolimbic dopamine (DA) system is implicated in the development and maintenance of alcohol drinking; however, the exact mechanisms by which DA regulates human alcohol consumption are unclear. This study assessed the distinct effects of alcohol-related cues and alcohol administration on striatal DA release in healthy humans. Methods:, Subjects underwent 3 PET scans with [11C]raclopride (RAC). Subjects were informed that they would receive either an IV Ringer's lactate infusion or an alcohol (EtOH) infusion during scanning, with naturalistic visual and olfactory cues indicating which infusion would occur. Scans were acquired in the following sequence: (1) Baseline Scan: Neutral cues predicting a Ringer's lactate infusion, (2) CUES Scan: Alcohol-related cues predicting alcohol infusion in a Ringer's lactate solution, but with alcohol infusion after scanning to isolate the effects of cues, and (3) EtOH Scan: Neutral cues predicting Ringer's, but with alcohol infusion during scanning (to isolate the effects of alcohol without confounding expectation or craving). Results:, Relative to baseline, striatal DA concentration decreased during CUES, but increased during EtOH. Conclusion:, While the results appear inconsistent with some animal experiments showing dopaminergic responses to alcohol's conditioned cues, they can be understood in the context of the hypothesized role of the striatum in reward prediction error, and of animal studies showing that midbrain dopamine neurons decrease and increase firing rates during negative and positive prediction errors, respectively. We believe that our data are the first in humans to demonstrate such changes in striatal DA during reward prediction error. [source]

A Microdialysis Profile of Dynorphin A1,8 Release in the Rat Nucleus Accumbens Following Alcohol Administration

ALCOHOLISM, Issue 6 2006
Peter W. Marinelli
Background: Pharmacological studies have implicated the endogenous opioid system in mediating alcohol intake. Other evidence has shown that alcohol administration can influence endorphinergic and enkephalinergic activity, while very few studies have examined its effect on dynorphinergic systems. The aim of the present study was to investigate the effect of alcohol administration or a mechanical stressor on extracellular levels of dynorphin A1,8 in the rat nucleus accumbens,a brain region that plays a significant role in the processes underlying reinforcement and stress. Methods: Male Sprague,Dawley rats were implanted with a microdialysis probe aimed at the shell region of the nucleus accumbens. Artificial cerebrospinal fluid was pumped at a rate of 1.5 ,L/min in awake and freely moving animals and the dialysate was collected at 30-minute intervals. In one experiment, following a baseline period, rats were injected intraperitoneally with either physiological saline or 1 of 3 doses of alcohol, 0.8, 1.6, or 3.2 g ethanol/kg body weight. In a second experiment, following a baseline period, rats were applied a clothespin to the base of their tail for 20 minutes. The levels of dynorphin A1,8 in the dialysate were analyzed with solid-phase radioimmunoassay. Results: Relative to saline-treated controls, an alcohol dose of 1.6 and 3.2 g/kg caused a transient increase in the extracellular levels of dynorphin A1,8 in the first 30 minutes of alcohol administration. However, the effect resulting from the high 3.2 g/kg dose was far more pronounced and more significant than with the moderate dose. There was no effect of tail pinch on dynorphin A1,8 levels in the nucleus accumbens. Conclusions: In this experiment, a very high dose of alcohol was especially capable of stimulating dynorphin A1,8 release in the nucleus accumbens. Dynorphin release in the accumbens has been previously associated with aversive stimuli and may thus reflect a system underlying the aversive properties of high-dose alcohol administration. However, the lack of effect of tail-pinch stress in the present study suggests that dynorphin A1,8 is not released in response to all forms of stressful/aversive stimuli. [source]

Gelatin "Shots" as a New Method for Alcohol Administration in a Laboratory Setting

ALCOHOLISM, Issue 3 2006
Elizabeth Ralevski
Background: This experiment was designed to compare gelatin "shots",a new procedure for administering alcohol in a laboratory setting,to the alcohol beverage method. We proceeded to test whether the two methods were comparable in terms of alcohol absorption, metabolism, and effects on mood and whether gelatin "shots" were better than the beverage in disguising alcohol in a blind, placebo comparison. Methods: Healthy volunteers participated in a two-phase trial. In the first phase they completed 2 days of testing during which the effects of alcohol,delivered in beverage (1 day) or gelatin "shots" (alternative day),on blood and breathalyzer concentrations and mood were assessed. In the second phase participants completed 2 days of testing and were asked to identify if samples contained alcohol or placebo. The presentation of alcohol and placebo and the presentation of beverage or gelatin "shots" were random. Results: In the first phase there was a significant time-by-condition interaction in the blood alcohol concentration. Two-and-a-half hours after the alcohol was administered, those given gelatin "shots" had slightly lower but statistically significant blood alcohol concentrations. There was a significant time effect for breathalyzer alcohol levels but no condition or condition-by-time interaction. There were no differences between the two methods on any of the subjective mood measures. In the second phase of the study there were differences in the ability to differentiate alcohol from placebo between the two conditions with significantly more participants making errors in the gelatin "shots" than in the beverage condition. Conclusions: Our findings indicate that gelatin "shots" are an effective method for delivering alcohol to humans in a laboratory setting. This method may be superior to the alcohol beverage mixture in a placebo-controlled design because gelatin "shots" mask the alcohol much better than a beverage and are easier to administer. [source]

Immunohistochemical Characterization of Hepatic Malondialdehyde and 4-Hydroxynonenal Modified Proteins During Early Stages of Ethanol-Induced Liver Injury

ALCOHOLISM, Issue 6 2003
Brante P. Sampey
Background: Chronic ethanol consumption is associated with hepatic lipid peroxidation and the deposition or retention of aldehyde-adducted proteins postulated to be involved in alcohol-induced liver injury. The purpose of this study was to characterize hepatocellular formation of aldehyde-protein adducts during early stages of alcohol-induced liver injury. Methods: Female Sprague Dawley® rats were subjected to the intragastric administration of a low-carbohydrate/high-fat total enteral nutrition diet or a total enteral nutrition diet containing ethanol for a period of 36 days. Indexes of hepatic responses to ethanol were evaluated in terms of changes in plasma alanine aminotransferase activity, hepatic histopathologic analysis, and induction of cytochrome P-4502E1 (CYP2E1). Immunohistochemical methods were used to detect hepatic proteins modified with malondialdehyde (MDA) or 4-hydroxynonenal (4-HNE) for subsequent quantitative image analysis. Results: After 36 days of treatment, rats receiving the alcohol-containing diet displayed hepatic histopathologies characterized by marked micro- and macrosteatosis associated with only minor inflammation and necrosis. Alcohol administration resulted in a 3-fold elevation of plasma alanine aminotransferase activity and 3-fold increases (p < 0.01) in hepatic CYP2E1 apoprotein and activity. Quantitative immunohistochemical analysis revealed significant (p < 0.01) 5-fold increases in MDA- and 4-HNE modified proteins in liver sections prepared from rats treated with alcohol. The MDA- or 4-HNE modified proteins were contained in hepatocytes displaying intact morphology and were colocalized primarily with microvesicular deposits of lipid. Aldehyde-modified proteins were not prevalent in parenchymal or nonparenchymal cells associated with foci of necrosis or inflammation. Conclusions: These results suggest that alcohol-induced lipid peroxidation is an early event during alcohol-mediated liver injury and may be a sensitizing event resulting in the production of bioactive aldehydes that have the potential to initiate or propagate ensuing proinflammatory or profibrogenic cellular events. [source]

The effects of binge drinking on college students' next-day academic test-taking performance and mood state

ADDICTION, Issue 4 2010
Jonathan Howland
ABSTRACT Aim To assess the effects of binge drinking on students' next-day academic test-taking performance. Design A placebo-controlled cross-over design with randomly assigned order of conditions. Participants were randomized to either alcoholic beverage [mean = 0.12 g% breath alcohol concentration (BrAC)] or placebo on the first night and then received the other beverage a week later. The next day, participants were assessed on test-taking, neurocognitive performance and mood state. Participants A total of 196 college students (,21 years) recruited from greater Boston. Setting The trial was conducted at the General Clinical Research Center at the Boston Medical Center. Measurements The Graduate Record Examinations© (GREs) and a quiz on a lecture presented the previous day measured test-taking performance; the Neurobehavioral Evaluation System (NES3) and the Psychomotor Vigilance Test (PVT) measured neurocognitive performance; and the Profile of Mood States (POMS) measured mood. Findings Test-taking performance was not affected on the morning after alcohol administration, but mood state and attention/reaction-time were affected. Conclusion Drinking to a level of 0.12 g% BrAC does not affect next-day test-taking performance, but does affect some neurocognitive measures and mood state. [source]

Antioxidant effect of 2-hydroxy-4-methoxy benzoic acid on ethanol-induced hepatotoxicity in rats

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2007
Nadana Saravanan
Alcoholic liver disease (ALD) is one of the most common diseases in society. A large number of studies are in progress to identify natural substances that are effective in reducing the severity of ALD. 2-Hydroxy-4-methoxy benzoic acid (HMBA), the active principle of Hemidesmus indicus, an indigenous Ayurvedic medicinal plant in India, is expected to significantly inhibit the development of liver injury in ethanol administration. It is expected to reduce the severity of liver damage in terms of body weight, hepatic marker enzymes, oxidative stress, antioxidant status and histological changes in ethanol-induced hepatotoxic rats. Hepatotoxicity was induced by administering 20% ethanol (5 g kg,1 daily) for 60 days to male Wistar rats, which resulted in significantly decreased body weight and an increase in liver-body weight ratio. The liver marker enzymes aspartate transaminase, alanine transaminase, alkaline phosphatase, ,-glutamyl transpeptidase and lactate dehydrogenase were elevated. In addition, the levels of plasma, erythrocyte and hepatic thiobarbituric acid reactive substances, hydroperoxides and conjugated dienes were also elevated in ethanol-fed rats as compared with those of the experimental control rats. Decreased activity of superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, vitamin C and ,-tocopherol was also observed on alcohol administration as compared with experimental control rats. HMBA was co-administered at a dose of 200 ,gkg,1 daily for the last 30 days of the experiment to rats with alcohol-induced liver injury, which significantly increased body weight, significantly decreased the liver-body weight ratio, transaminases, alkaline phosphatase, ,-glutamyl transpeptidase and lactate dehydrogenase, significantly decreased the levels of lipid peroxidative markers, significantly elevated the activity of enzymic and non-enzymic antioxidants in plasma, erythrocytes and liver and also increased levels of plasma and liver vitamin C and ,-tocopherol at the end of the experimental period as compared with untreated ethanol-administered rats. The histological changes were also in correlation with the biochemical findings. The results suggest that HMBA administration may afford protection against ethanol-induced liver injury in rats. [source]

The pharmacological potential of Sorbus commixta cortex on blood alcohol concentration and hepatic lipid peroxidation in acute alcohol-treated rats

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2006
Syng-Ook Lee
The effect of Sorbus commixta cortex, a traditional herbal medicine used for the treatment of bronchitis, gastritis and dropsy, on blood alcohol concentration (BAC) and hepatic lipid peroxidation was examined in acute alcohol-treated rats. A 30-min pretreatment with a methanol extract of S. commixta cortex (SC) at concentrations higher than 200 mg kg,1 resulted in a significant decrease in BAC and the ethyl acetate fraction (SE) of the extract showed the highest potency, with a maximum of a 46% decrease at 150 mg kg,1 2h after alcohol administration (3.0 g kg,1) compared with the control group (P < 0.005). The rapid reduction in BAC did not appear to be due to the protection or activation of hepatic alcohol dehydrogenase (ADH) activity by SE. Hepatic malondialdehyde (MDA) levels were significantly increased by acute alcohol administration within 6h, although pretreatment with the SE caused a significant decrease in MDA levels compared with alcohol treatment alone. Hepatic glutathione (GSH) levels and superoxide dismutase (SOD) activity remained unchanged by alcohol, SE alone or by the combined treatment of alcohol and SE. However, catalase activity was significantly reduced by acute alcohol administration and pretreatment with the SE led to significant protection of its activity. These results suggest that pretreatment with SE reduces hepatic lipid peroxidation by decreasing the bioavailability of alcohol and its oxidative metabolites, such as H2O2, at least partly, through the protection of hepatic catalase in acute alcohol-treated rats. [source]

Naltrexone Selectively Elevates GABAergic Neuroactive Steroid Levels in Heavy Drinkers With the ASP40 Allele of the OPRM1 Gene: A Pilot Investigation

ALCOHOLISM, Issue 8 2010
Lara A. Ray
Background:, Preclinical studies have implicated GABAergic neurosteroids in behavioral responses to alcohol. Naltrexone is thought to blunt the reinforcing effects of alcohol, and a few studies have found that the effects of naltrexone are moderated by the Asn40Asp polymorphisms of the OPRM1 gene. The present study seeks to integrate these lines of research by testing (i) the moderating role of the functional Asn40Asp polymorphism of the OPRM1 gene on naltrexone-induced alternations in GABAergic neurosteroid levels, namely (3,,5,)-3-hydroxypregnan-20-one (allopregnanolone, ALLO); and (ii) the combined effects of naltrexone or genotype with alcohol administration on neurosteroid levels in a sample of at-risk drinkers. Methods:, Participants were 32 (9 females) nontreatment-seeking heavy drinkers who completed a placebo-controlled laboratory study of naltrexone (50 mg/d for 3 days) and provided complete sets of serum samples for ALLO assays before and after alcohol administration under both naltrexone and placebo conditions. Results:, Naltrexone treatment raised ALLO levels among carriers of the Asp40 allele, but not homozygotes for the Asn40 allele. The Asn40Asp polymorphism did not moderate effects of naltrexone on cortisol levels. Ethanol infusion modestly reduced ALLO levels in all subjects, independent of genotype or naltrexone exposure. Conclusions:, Naltrexone increased ALLO levels among individuals with the Asn40Asp allele suggesting a potential neurosteroid contribution to the neuropharmacological effects of naltrexone among Asp40 carriers. [source]

ADH1B*3 and Response to Alcohol in African-Americans

ALCOHOLISM, Issue 7 2010
Denis M. McCarthy
Background: Variations in the alleles for the alcohol-metabolizing enzymes have been shown to influence risk for alcohol dependence. One variant, ADH1B*3, is observed almost exclusively in populations of African ancestry and has been shown to be associated with reduced rates of alcohol dependence. We conducted an alcohol challenge study to test whether ADH1B*3 is associated with differences in subjective and physiological response to alcohol. Method: We administered a moderate dose of alcohol (0.72 g/kg for males, 0.65 g/kg for females) to a sample of African-American young adults (n = 91; ages 21 to 26). Participants were genotyped for ADH1B, as well as additional polymorphisms that might contribute to alcohol response. Breath alcohol concentration, self-reported sedation and stimulation, and pulse rate were assessed prior to alcohol administration and for 2.5 hours following administration. Results: ADH1B*3 was associated with higher levels of sedation and a sharper increase in pulse rate immediately following alcohol consumption. Conclusions: These findings suggest that the lower rates of alcohol dependence in those with ADH1B*3 alleles may be because of differences in alcohol response, particularly increased sedation. [source]

,-Endorphin Mediates Behavioral Despair and the Effect of Ethanol on the Tail Suspension Test in Mice

ALCOHOLISM, Issue 6 2010
Elizabeth T. Barfield
Background:, The opioid peptide ,-endorphin (,-E) is synthesized and released in response to stressful stimuli as well as acute alcohol administration. The release of ,-E following exposure to an inescapable aversive situation may mediate behaviors that contribute to allostasis of the stress response. The present study examines the effects of ,-E on immobility in assays involving inescapable stress, both under basal conditions and after acute administration of EtOH. Methods:, Female and male transgenic mice with varying capacities to translate ,-E were subjected to either the forced swim (FST, Experiment 1) or the tail suspension test (TST, Experiment 2). In Experiment 3, mice were divided into three groups based on hormonal status (male, female-estrous, and female-nonestrous) and injected with either 1 g/kg EtOH or equivolume saline 14 minutes prior to behavioral assessment on the TST. Results:, Experiments 1 and 2 demonstrated a direct relationship between ,-E levels and immobility. There were also sex differences in behavior in these tests, with males displaying more immobility than females. A main effect of genotype in Experiment 3 replicated findings in Experiments 1 and 2. There was also an effect of EtOH (increasing immobility) and a significant interaction reflecting a particularly robust effect of the drug in mice with low ,-E. In addition, there were interactions between ,-E, EtOH effects, and hormonal status. Conclusions:, These findings support the contention that ,-E moderates behavioral responses to stressful stimuli and suggest a role for this peptide in coping behavior. Furthermore, the effects of EtOH on the response to stress may be mediated by ,-E. Sex differences in this influence may contribute to sex differences in disease susceptibility and expression. [source]

Neuropeptide S Receptor Gene Expression in Alcohol Withdrawal and Protracted Abstinence in Postdependent Rats

ALCOHOLISM, Issue 1 2010
Barbara Ruggeri
Background:, Alcoholism is a chronic disease characterized by frequent intoxications followed by withdrawal episodes and relapse to alcohol use. Neuroplastic changes associated with these intoxication and withdrawal cycles are thought to play a key role in disease progression. Recently, it has been shown that neuropeptide S (NPS), a newly deorphanized neuropeptide receptor system, facilitates relapse to alcohol seeking in laboratory animals. Given that a history of ethanol intoxication may increase vulnerability to alcohol addiction, we sought to determine whether NPS receptor (NPSR) gene expression is altered during withdrawal. Methods:, Rats were subjected to 1 week of intoxication by oral alcohol administration. NPSR gene expression was analyzed by in situ hybridization in rats 12 hours and 7 days after the last alcohol administration. To investigate the functional significance of NPSR system adaptation following protracted withdrawal 7 days after intoxication, we tested the anxiolytic-like properties of NPS in nondependent and postdependent rats using the shock probe defensive burying test (DB). Results:, At both time points, increased NPSR gene expression was observed in several brain areas, including the endopiriform nucleus, the motor cortex, and the medial amygdaloid nucleus. Moderate increases in gene expression were also found in the lateral hypothalamus, paraventricular nucleus, basolateral and central amygdala. Differences from control animals were more pronounced after 7 days of abstinence. The upregulation of the NPSR system at this time point was confirmed by functional data indicating that intracerebroventricular (ICV) NPS administration (0.0, 0.3, and 0.1 nmol/rat) elicits more pronounced anxiolytic effects in postdependent animals than in controls subjected to the electric shock probe DB test. Conclusions:, Neuropeptide S receptor mRNA expression is increased in different brain areas of postdependent rats; as shown in the DB test, this expression change is functionally relevant. [source]

Intravenous Ethanol Infusions Can Mimic the Time Course of Breath Alcohol Concentrations Following Oral Alcohol Administration in Healthy Volunteers

A Recent Perspective on Alcohol, Immunity, and Host Defense

ALCOHOLISM, Issue 2 2009
Gyongyi Szabo
Background:, Multiple line of clinical and experimental evidence demonstrates that both acute, moderate, and chronic, excessive alcohol use result in various abnormalities in the functions of the immune system. Methods:, Medline and Pubmed databases were used to identify published reports with particular interest in the period of 2000,2008 in the subject of alcohol use, infection, inflammation, innate, and adaptive immunity. Results:, This review article summarizes recent findings relevant to acute or chronic alcohol use-induced immunomodulation and its consequences on host defense against microbial pathogens and tissue injury. Studies with in vivo and in vitro alcohol administration are both discussed. The effects of alcohol on lung infections, trauma and burn injury, liver, pancreas, and cardiovascular diseases are evaluated with respect to the role of immune cells. Specific changes in innate immune response and abnormalities in adaptive immunity caused by alcohol intake are detailed. Conclusion:, Altered inflammatory cell and adaptive immune responses after alcohol consumption result in increased incidence and poor outcome of infections and other organ-specific immune-mediated effects. [source]

When What You See Isn't What You Get: Alcohol Cues, Alcohol Administration, Prediction Error, and Human Striatal Dopamine

Maturation-Dependent Alcohol Resistance in the Developing Mouse: Cerebellar Neuronal Loss and Gene Expression During Alcohol-Vulnerable and -Resistant Periods

ALCOHOLISM, Issue 8 2008
Bahri Karaçay
Background:, Alcohol abuse during pregnancy injures the fetal brain. One of alcohol's most important neuroteratogenic effects is neuronal loss. Rat models have shown that the cerebellum becomes less vulnerable to alcohol-induced neuronal death as it matures. We determined if maturation-dependent alcohol resistance occurs in mice and compared patterns of gene expression during the alcohol resistant and sensitive periods. Methods:, Neonatal mice received alcohol daily over postnatal day (PD) 2 to 4 or PD8 to 10. Purkinje cells and granule cells were quantified on PD25. The temporal expression patterns of 4 neuro-developmental genes and 3 neuro-protective genes in the cerebellum were determined daily over PD0 to 15 to determine how gene expression changes as the cerebellum transitions from alcohol-vulnerable to alcohol-resistant. The effect of alcohol on expression of these genes was determined when the cerebellum is alcohol sensitive (PD4) and resistant (PD10). Results:, Purkinje and granule cells were vulnerable to alcohol-induced death at PD2 to 4, but not at PD8 to 10. Acquisition of maturation-dependent alcohol resistance coincided with changes in the expression of neurodevelopmental genes. The vulnerability of cerebellar neurons to alcohol toxicity declined in parallel with decreasing levels of Math1 and Cyclin D2, markers of immature granule cells. Likewise, the rising resistance to alcohol toxicity paralleled increasing levels of GABA ,-6 and Wnt-7a, markers of mature granule neurons. Expression of growth factors and genes with survival promoting function (IGF-1, BDNF, and cyclic AMP response element binding protein) did not rise as the cerebellum transitioned from alcohol-vulnerable to alcohol-resistant. All 3 were expressed at substantial levels during the vulnerable period and were not expressed at higher levels later. Acute alcohol exposure altered the expression of neurodevelopmental genes and growth factor genes when administered either during the alcohol vulnerable period or resistant period. However, the patterns in which gene expression changed varied among the genes and depended on timing of alcohol administration. Conclusions:, Mice have a temporal window of vulnerability in the first week of life, during which cerebellar neurons are more sensitive to alcohol toxicity than during the second week. Expression of genes governing neuronal maturation changes in synchrony with the acquisition of alcohol resistance. Growth factors do not rise as the cerebellum transitions from alcohol-vulnerable to alcohol-resistant. Thus, a process intrinsic to neuronal maturation, rather than rising levels of growth factors, likely underlies maturation-dependent alcohol resistance. [source]

Is the Strength of Implicit Alcohol Associations Correlated with Alcohol-induced Heart-rate Acceleration?

ALCOHOLISM, Issue 8 2006
Esther Van Den Wildenberg
Background: Heart rate (HR) acceleration during the ascending limb of the blood alcohol curve has proven to be a reliable measure of the sensitivity to the activating effects of alcohol. In this study, we investigated the correlation between an ethanol-induced cardiac change and the strength of implicit alcohol-related arousal and approach associations and attentional bias for alcohol-related stimuli in heavy drinkers. These 3 types of implicit alcohol-related cognitions have been proposed to reflect the strength of incentive sensitization that is experienced after repeated alcohol use. Methods: Forty-eight heavy drinking men performed a modified version of the Implicit Association Test (IAT) to measure their implicit alcohol arousal and approach,avoidance associations. A modified version of the emotional Stroop was used to measure attentional bias for alcohol-related stimuli (blocked and unblocked). Next, a high dose of alcohol (1.0 mL/kg body weight 95% USP alcohol) was administered in a short period of time. Resting baseline HR, blood alcohol concentrations, mood, and craving for alcohol were assessed before alcohol administration and for 2 hours post,alcohol consumption. Results: Contrary to our hypothesis, a negative association was found between implicit arousal associations and alcohol-induced HR change. This indicates that strong arousal associations were correlated with a decrease in alcohol-induced HR. Approach associations and attentional bias were not correlated with alcohol-induced HR change, but both were correlated positively with each other. Conclusions: Alcohol-arousal associations and other implicit cognitions (attentional bias, approach associations) are not positively related to individual differences in the sensitivity to alcohol's activating effects, at least not in the present sample consisting primarily of family history-negative heavy drinkers. [source]

Effects of Alcohol on Sleep and the Sleep Electroencephalogram in Healthy Young Women

ALCOHOLISM, Issue 6 2006
Eliza Van Reen
Background: Although the association between sleep and alcohol has been of interest to scientists for decades, the effects of alcohol on sleep and sleep electroencephalogram (EEG) have not been extensively studied in women. Our specific aim was to determine whether sleep stage variables and/or spectral characteristics of the sleep EEG are altered by alcohol administration in women. Methods: Changes of sleep and the sleep EEG were investigated after administration of a moderate dose of alcohol (0.49 g/kg) in the hour before bedtime compared with placebo in young healthy women. After approximately 2 weeks at home on a fixed 8.5- or 9-hour stabilization sleep schedule, sleep was continuously recorded by polysomnography for 3 consecutive nights [adaptation, placebo, alcohol (mean breath alcohol concentration 0.043 g/% before bedtime)] in the laboratory in 7 women (ages 22,25, mean=23.5, SD=1 year). Sleep stages were scored according to conventional criteria. Electroencephalogram power spectra of the bipolar derivations Fz/Cz (anterior) and Pz/Oz (posterior) were calculated using a fast Fourier transform routine. Results: Only few changes in sleep and the sleep EEG were observed. Across the entire night rapid eye movement (REM) sleep decreased, while minutes of stage 4 sleep were increased in the first 2-hour interval on alcohol nights compared with placebo nights. Spectral analysis of the EEG showed increased power in the , range (9,11 Hz) during all-night non-REM (NREM) sleep in anterior derivations after alcohol compared with placebo. Differences in spectral EEG power were also present in 2-hour intervals of NREM sleep; in particular, EEG power was increased on the alcohol night for frequency bins within the , range in anterior derivations and within the , range (3,4 Hz) in posterior derivations during the initial part of the night. Conclusions: A moderate dose of alcohol just before bedtime resulted in a short-lived increase in sleep intensity. A limitation of the study, however, was that only a single dose of alcohol was used to examine the effects of alcohol on sleep. [source]

A Microdialysis Profile of Dynorphin A1,8 Release in the Rat Nucleus Accumbens Following Alcohol Administration

ALDH2 Status, Alcohol Expectancies, and Alcohol Response: Preliminary Evidence for a Mediation Model

ALCOHOLISM, Issue 11 2001
Denis M. McCarthy
Background: A genetic variant in the alcohol-metabolizing enzyme (aldehyde dehydrogenase;ALDH2*2 allele), common in individuals of Asian heritage, has been associated with both physiologic response to alcohol and alcohol consumption. Prior research has also demonstrated that those with ALDH2*2 alleles have lower positive alcohol expectancies than those without these alleles. This preliminary study was designed to test whether the level of response to alcohol is the mechanism by which ALDH2 status may affect alcohol expectancies. Methods: Data were collected from 32 Asian American college students (14 women and 18 men). By use of a randomized, double-blind design, participants were administered oral placebo and alcohol at separate laboratory sessions. Data included blood tests to establish ALDH2 status, questionnaire measures of demographic information and alcohol expectancy, and several physiologic measures collected after placebo and alcohol administration. Results: ALDH2 status was related to alcohol response measures for both men and women. ALDH2 status was also related to tension reduction expectancies for women and to expectancies for cognitive behavioral impairment for men. In the male sample, the ALDH2/expectancy relationship was fully explained by the level of response to alcohol. Conclusions: These results represent a first step in understanding the mechanisms by which genetic factors, such as ALDH2 status, can affect alcohol-related learning. [source]

Serum 6-Beta-Naltrexol Levels Are Related to Alcohol Responses in Heavy Drinkers

ALCOHOLISM, Issue 9 2000
Mary E. McCaul
Background: There is strong evidence for the role of the endogenous opioid system in alcohol reinforcement and consumption; however, recent human laboratory studies and clinical trials have reported mixed effects of naltrexone (a nonselective opioid antagonist) on alcohol-related behaviors. This paper reports a secondary data analysis of a human laboratory study that examines the relationship between serum levels of 6-beta-naltrexol, the major, biologically active metabolite of naltrexone, and subjective effects of alcohol. Methods: The study used a within-subjects design to examine the effects of naltrexone (0, 50, and 100 mg/day) on subjective responses to alcohol (none, moderate, and high dose) in heavy drinkers (n= 23). Each subject received three doses of naltrexone in random order; each naltrexone dose was administered over an 8 day period on an inpatient unit, with a 1 week outpatient washout between doses. After stabilization at each of the naltrexone doses, subjects participated in three alcohol challenge sessions (none, moderate, and high dose) in random order; thus, each subject participated in a total of nine alcohol administration sessions. Results: Doubling the naltrexone dose (50 vs. 100 mg/day) doubled the mean serum 6-beta-naltrexol levels. At each naltrexone dose, there was a 4-fold range in 6-beta-naltrexol levels across subjects. Before alcohol administration, higher 6-beta-naltrexol levels were associated with higher ratings of sedation. After high-dose alcohol administration, higher 6-beta-naltrexol levels were associated with significantly lower ratings of liking and best effects. Conclusions: These findings provide further evidence of the involvement of the opioid system in the modulation of alcohol effects and suggest that serum 6-beta-naltrexol concentrations may be important in predicting therapeutic response to naltrexone. [source]

Adaptation of Mesenteric Collecting Lymphatic Pump Function Following Acute Alcohol Intoxication

MICROCIRCULATION, Issue 7 2010
FLAVIA M. SOUZA-SMITH
Please cite this paper as: Souza-Smith, Kurtz, Molina and Breslin (2010). Adaptation of Mesenteric Collecting Lymphatic Pump Function Following Acute Alcohol Intoxication. Microcirculation17(7), 514,524. Abstract Objective:, Acute alcohol intoxication increases intestinal lymph flow by unknown mechanisms, potentially impacting mucosal immunity. We tested the hypothesis that enhanced intrinsic pump function of mesenteric lymphatics contributes to increased intestinal lymph flow during alcohol intoxication. Methods:, Acute alcohol intoxication was produced by intragastric administration of 30% alcohol to conscious, unrestrained rats through surgically implanted catheters. Time-matched controls received either no bolus, vehicle, or isocaloric dextrose. Thirty minutes after alcohol administration, rats were anesthetized and mesenteric collecting lymphatics were isolated and cannulated to study intrinsic pumping parameters. In separate experiments, mesenteric lymphatics were isolated to examine direct effects of alcohol on intrinsic pump activity. Results:, Lymphatics isolated from alcohol-intoxicated animals displayed significantly decreased CF compared to the dextrose group, elevated SVI versus all other groups, and decreased myogenic responsiveness compared to sham. Elevating pressure from 2 to 4 cm H2O increased the volume flow index 2.4-fold in the alcohol group versus 1.4-fold for shams. Isolated lymphatics exposed to 20 mM alcohol had reduced myogenic tone, without changes in CF or SVI. Conclusions:, Alcohol intoxication enhances intrinsic pumping by mesenteric collecting lymphatics. Alcohol directly decreases lymphatic myogenic tone, but effects on phasic contractions occur by an unidentified mechanism. [source]

Alcohol tolerance and nicotine cross-tolerance in adolescent mice

ADDICTION BIOLOGY, Issue 2 2001
Marcelo F. Lopez
The present experiment was designed to evaluate the development of tolerance to alcohol and cross-tolerance to nicotine in adolescent mice. C57BL/6J mice (30,40 days old) were injected IP with alcohol (2.5 g/kg) for 4 consecutive days. A control group received four saline injections. On the test day, all subjects received an alcohol injection. Tolerance to alcohol's hypothermic effect was observed. Mice (male and female) exposed to alcohol for the 4 previous days showed less hypothermic response to an alcohol challenge than animals injected for 4 days with saline and then challenged with alcohol. Tolerance to alcohol's motor incoordinating effects and differences in blood alcohol concentrations were not observed. Thirty days following alcohol treatment, the same mice received a single nicotine injection (1 mg/kg) to assess cross-tolerance. Nicotine's effect on locomotor activity (open field test) and rectal temperature varied as a function of prior adolescent alcohol exposure and gender. Specifically, female mice who had been exposed to alcohol administrations were more resistant to nicotine's effect on locomotion and temperature than saline-treated animals. In summary, these data demonstrate that adolescent mice develop tolerance to some, but not all, alcohol-induced responses, and that female mice are cross-tolerant to nicotine's effects on temperature and activity. [source]

Disruption of Maternal Behavior by Alcohol Intoxication in the Lactating Rat: A Behavioral and Metabolic Analysis

ALCOHOLISM, Issue 8 2002
Marta Yanina Pepino
Background Preweanling rats exhibit clear behavioral signs of distress after interacting with an alcohol-intoxicated dam. Interestingly, behavioral reactivity of infants to the experience of alcohol in the nursing context decreases as a function of repeated alcohol administrations to the mother. In this study, maternal activities were examined when dams were exposed to repeated administrations of a subnarcoleptic alcohol dose. Maternal changes in alcohol metabolism were also analyzed as a function of repeated exposures to the drug. Methods During postpartum days 3, 5, 7, 9, 11, and 13, nursing dams received an intragastric administration of either 2.5 g/kg of alcohol or water. Maternal behaviors were evaluated (experiment 1). Blood alcohol levels (BALs) of the dams were determined on postpartum day 16 after all mothers received either an intragastric (experiment 2) or an intraperitoneal (experiment 3) dose of alcohol. The doses used (2.5 g/kg intragastrically and 1.5 g/kg intraperitoneally) were chosen because they promote similar peak BALs in dams naive to alcohol. Results Maternal behaviors were strongly affected by the state of intoxication. Nevertheless, these disruptions clearly subsided with progression of alcohol-related experiences (experiment 1). Chromatographic analysis of alcohol metabolism indicated the development of tolerance in dams that had prior experience with alcohol (experiment 2). Changes in BALs as a function of prior experience with alcohol seemed related to first-pass alcohol metabolism rather than hepatic oxidative processes of the drug (experiments 2 and 3). Conclusions When the dam first experiences a moderate state of alcohol intoxication, maternal behaviors are uniformly disrupted. Subsequent exposures to alcohol lead to maternal metabolic tolerance. In conjunction with previous studies, these data indicate that infantile reactivity to alcohol is dependent on how the members of the dam/pup dyad express or perceive ethanol's postabsorptive effects. [source]