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Alcohol Self-administration (alcohol + self-administration)

Distribution by Scientific Domains

Medical Sciences	88%
Life Sciences	11%

Selected Abstracts

Motivation for Alcohol Becomes Resistant to Quinine Adulteration After 3 to 4 Months of Intermittent Alcohol Self-Administration

ALCOHOLISM, Issue 9 2010
Frederic W. Hopf
Background:, Continued consumption of alcohol despite deleterious consequences is a hallmark of alcoholism and represents a critical challenge to therapeutic intervention. Previous rat studies showed that enduring alcohol self-administration despite pairing alcohol with normally aversive stimuli was only observed after very long-term intake (>8 months). Aversion-resistant alcohol intake has been previously interpreted to indicate pathological or compulsive motivation to consume alcohol. However, given the time required to model compulsive alcohol seeking in previous studies, there is considerable interest in developing more efficient and quantitative rodent models of aversion-resistant alcohol self-administration. Methods:, Outbred Wistar rats underwent 3 to 4 months or approximately 1.5 months of intermittent, home-cage, two-bottle access (IAA) to 20% alcohol (v/v) or water. Then, after brief operant training, the effect of the bitter-tasting quinine (0.1 g/l) on the motivation to seek alcohol was quantified via progressive ratio (PR). Motivation for quinine-adulterated 2% sucrose under PR was assayed in a separate cohort of 3 to 4 months IAA rats. The effects of quinine on home-cage alcohol consumption in IAA rats and rats with continuous access to alcohol were also examined. Finally, a dose,response for quinine taste preference in IAA and continuous-access animals was determined. Results:, Motivation for alcohol after 3 to 4 months IAA, measured using an operant PR procedure, was not altered by adulteration of alcohol with 0.1 g/l quinine. In contrast, after 3 to 4 months of IAA, motivation for sucrose under PR was significantly reduced by adulteration of sucrose with 0.1 g/l quinine. In addition, motivation for alcohol after only approximately 1.5 months IAA was significantly reduced by adulteration of alcohol with 0.1 g/l quinine. Furthermore, home-cage alcohol intake by IAA rats was insensitive to quinine at concentrations (0.01, 0.03 g/l) that significantly reduced alcohol drinking in animals with continuous access to alcohol. Finally, no changes in quinine taste preference after 3 to 4 months IAA or continuous access to alcohol were observed. Conclusions:, We have developed a novel and technically simple hybrid operant/IAA model in which quinine-resistant motivation for alcohol is evident after an experimentally tractable period of time (3 to 4 months vs. 8 months). Quinine dramatically reduced sucrose and water intake by IAA rats, indicating that continued responding for alcohol in IAA rats despite adulteration with the normally aversive quinine might reflect maladaptive or compulsive motivation for alcohol. This model could facilitate identification of novel therapeutic interventions for pathological alcohol seeking in humans. [source]

Abstinence From Moderate Alcohol Self-Administration Alters Progenitor Cell Proliferation and Differentiation in Multiple Brain Regions of Male and Female P Rats

ALCOHOLISM, Issue 1 2009
Jun He
Background:, Acute and chronic ethanol exposure has been found to decrease hippocampal neurogenesis, reduce dendritic differentiation of new neurons, and increase cell death. Interestingly, abstinence from such treatment increases hippocampal neurogenesis and microglial genesis across several brain regions. The goal of the current investigation was to study cellular alterations on neuro- and cell-genesis during abstinence following alcohol self-administration using alcohol-preferring rats (P rats). Methods:, Male and female P rats were given the choice of drinking 10% alcohol in water or pure water for 7 weeks. Social interaction behavioral assessments were conducted at 5 hours upon removal of alcohol, followed by bromo-deoxyuridine (BrdU, 150 mg/kg × 1/d × 14 d) injections to label proliferating cells. Animals were then killed 4 weeks later to conduct immunohistochemical and confocal analyses using antibodies against BrdU and other phenotypic markers (NeuN for mature neurons; Iba-1 for microglia; GFAP for astrocytes; and NG2 for oligodendrocyte progenitors). Results:, Mild alcohol withdrawal anxiety was detected by reduction in social interactions. The number of hippocampal BrdU+ cells was increased approximately 50% during alcohol abstinence (26 ± 2.8 in controls vs. 39 ± 4 in alcohol group). BrdU+ cells were also increased in the substantia nigra (SN) approximately 65% in the alcohol abstinent group (12 ± 1 in controls vs. 19 ± 1.5 in alcohol group). No gender differences were found. Confocal analyses indicated that approximately 75% of co-localization of BrdU+ cells with NeuN in the hippocampal dentate gyrus (DG) resulting a net increase in neurogenesis in the alcohol abstinent group compared to controls. In cingulum, greater proportion of BrdU+ cells were co-localized with NG2 in the alcohol abstinent group indicating increased differentiation toward oligodendrocyte progenitors in both genders. However, the phenotype of the BrdU+ cells in SN and other brain regions were not identified by NeuN, Iba-1, GFAP, or NG2 suggesting that these BrdU+ cells probably remain in a nondifferentiated stage. Conclusions:, These data indicate that abstinence from moderate alcohol drinking increases hippocampal neurogenesis, cingulate NG2 differentiation, and SN undifferentiated cell proliferation in both males and females. Such cellular alteration during abstinence could contribute to the spontaneous partial restoration of cognitive deficits upon sobriety. [source]

Overlapping Peptide Control of Alcohol Self-Administration and Feeding

ALCOHOLISM, Issue 2 2004
Todd E. Thiele
Abstract: This article represents the proceedings of a symposium at the 2003 annual meeting of the Research Society on Alcoholism in Fort Lauderdale, FL. The organizers and chairpersons were Mark Egli and Todd E. Thiele. The presentations were (1) Voluntary alcohol consumption is modulated by central melanocortin receptors, by Todd E. Thiele; (2) Central infusion of neuropeptide Y reduces alcohol drinking in alcohol-preferring P rats, by Robert B. Stewart and Nancy E. Badia-Elder; (3) The gut peptide cholecystokinin controls alcohol intake in Sardinian alcohol-preferring rats, by Nori Geary and Maurizio Massi; and (4) Hypothalamic galanin: a possible role in excess alcohol drinking, by Sarah F. Leibowitz and Bartley G. Hoebel. [source]

Impact of Sex: Determination of Alcohol Neuroadaptation and Reinforcement

ALCOHOLISM, Issue 2 2006
Kristine M. Wiren
This article represents the proceedings of a symposium at the Research Society on Alcoholism meeting in Santa Barbara, California. The organizers/chairs were Kristine M. Wiren and Deborah A. Finn. Following a brief introduction by Deborah Finn, the presentations were (1) The Importance of Gender in Determining Expression Differences in Mouse Lines Selected for Chronic Ethanol Withdrawal Severity, by Kristine M. Wiren and Joel G. Hashimoto; (2) Sex Differences in Ethanol Withdrawal Involve GABAergic and Stress Systems, by Paul E. Alele and Leslie L. Devaud; (3) The Influence of Sex on Ethanol Consumption and Reward in C57BL/6 Mice, by Kimber L. Price and Lawrence D. Middaugh; and (4) Sex Differences in Alcohol Self-administration in Cynomolgus Monkeys, by Kathleen A. Grant. [source]

Alcohol self-administration acutely stimulates the hypothalamic-pituitary-adrenal axis, but alcohol dependence leads to a dampened neuroendocrine state

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2008
Heather N. Richardson
Abstract Clinical studies link disruption of the neuroendocrine stress system with alcoholism, but remaining unknown is whether functional differences in the hypothalamic-pituitary-adrenal (HPA) axis precede alcohol abuse and dependence or result from chronic exposure to this drug. Using an operant self-administration animal model of alcohol dependence and serial blood sampling, we show that long-term exposure to alcohol causes significant impairment of HPA function in adult male Wistar rats. Acute alcohol (voluntary self-administration or experimenter-administered) stimulated the release of corticosterone and its upstream regulator, adrenocorticotropic hormone, but chronic exposure sufficient to produce dependence led to a dampened neuroendocrine state. HPA responses to alcohol were most robust in ,low-responding' non-dependent animals (averaging < 0.2 mg/kg/session), intermediate in non-dependent animals (averaging ,0.4 mg/kg/session), and most blunted in dependent animals (averaging ,1.0 mg/kg/session) following several weeks of daily 30-min self-administration sessions, suggesting that neuroendocrine tolerance can be initiated prior to dependence and relates to the amount of alcohol consumed. Decreased expression of corticotropin-releasing factor (CRF) mRNA expression in the paraventricular nucleus of the hypothalamus and reduced sensitivity of the pituitary to CRF may contribute to, but do not completely explain, neuroendocrine tolerance. The present results, combined with previous studies, suggest that multiple adaptations to stress regulatory systems may be brought about by excessive drinking, including a compromised hormonal response and a sensitized brain stress response that together contribute to dependence. [source]

Environmental Cues, Alcohol Seeking, and Consumption in Baboons: Effects of Response Requirement and Duration of Alcohol Abstinence

ALCOHOLISM, Issue 12 2006
Elise M. Weerts
Background: Environmental stimuli (cues) that have been paired with alcohol drinking may evoke classically conditioned states that in turn influence alcohol consumption and relapse to heavy drinking. Animal models using chained schedules of alcohol reinforcement may be useful for examining such complex interactions. Methods: Alcohol drinking was established in 4 baboons. A sequence of lights and tones was presented during daily 3-hour sessions. First, cues were presented alone and no programmed contingencies were in effect. Second, cues were paired with 3 linked components consisting of different behavioral contingencies leading to and concluding with access to alcohol for self-administration in the last component (i.e., a chained schedule of alcohol reinforcement). Third, the effects of withholding alcohol access (i.e., forced abstinence) and increasing the number of lever responses required per drink were evaluated. Results: Cues paired with a chained schedule of alcohol reinforcement engendered behaviors that brought baboons into contact with alcohol-related cues and occasioned operant responding that facilitated access to alcohol (alcohol seeking) during components that preceded alcohol access. Increasing the response requirement for each drink decreased the number of drinks and volume of alcohol consumed, but did not alter alcohol seeking. On the first session after 14 days of alcohol abstinence, latency to complete the operant requirement that produced alcohol access was decreased while both alcohol self-administration and volume of alcohol consumed were increased. Conclusions: Alcohol self-administration and consumption were sensitive to increases in response requirement and duration of alcohol abstinence, while seeking was only enhanced by duration of alcohol abstinence. This animal model may be useful to further examine the interactions between environmental cues and behaviors associated with seeking and consumption of alcohol and to evaluate the efficacy of potential alcohol treatment drugs on these behaviors. [source]

Craving: what can be done to bring the insights of neuroscience, behavioral science and clinical science into synchrony

ADDICTION, Issue 8s2 2000
Roger E. Meyer
Alcohol self-administration behavior is the common thread that is necessary to bring the insights of neuroscience, behavioral science and clinical science into synchrony around the concept of craving. Animal models should address the molecular and cellular changes that take place in behaviorally relevant brain regions of rats consequent to chronic self-administration of ethanol. Animal models can focus on the biology of the anticipatory state in alcohol preferring/consuming rats, as well as studies of the effects of possible medications on this state in the animal model, on actual alcohol consuming behavior, and on the residual effects of chronic alcohol on the non-human mammalian brain. In human studies of craving, cue-reactivity in the absence of the opportunity to drink alcohol does not have the same salience as cue-reactivity in which drinking is possible. Moreover, actual drinking behavior serves to validate self-reports of craving. Studies of limited alcohol self-administration in the laboratory are an essential element in screening new medications for the treatment of alcoholism. Studies to date suggest no adverse reaction to the participation of alcoholic subjects in limited alcohol self-administration studies, but the research community should continue to monitor carefully the outcomes of alcohol-dependent subjects who participate in this type of research, and efforts should always be made to encourage these subjects to enter active treatment. In outpatient clinical trials of new treatments for alcoholism, the assessment of craving should include queries regarding symptoms and signs of protracted abstinence such as sleep disturbances, as well as questions regarding situational craving. Field observations of alcoholics in their favorite drinking environments would contribute greatly to our understanding of the real-world phenomenology of craving. [source]

Overexpression of dopamine D2 receptors reduces alcohol self-administration

JOURNAL OF NEUROCHEMISTRY, Issue 2 2001
CORRECTION
No abstract is available for this article. [source]

Motivation for Alcohol Becomes Resistant to Quinine Adulteration After 3 to 4 Months of Intermittent Alcohol Self-Administration

Increased Perioculomotor Urocortin 1 Immunoreactivity in Genetically Selected Alcohol Preferring Rats

ALCOHOLISM, Issue 11 2009
Irina Fonareva
Introduction:, Urocortin 1 (Ucn 1) is an endogenous peptide related to the corticotropin-releasing factor (CRF). Ucn 1 is mainly expressed in the perioculomotor area (pIII), and its involvement in alcohol self-administration is well confirmed in mice. In other species, the relationship between the perioculomotor Ucn 1-containing population of neurons (pIIIu) and alcohol consumption needs further investigation. The pIII also has a significant subpopulation of dopaminergic neurons. Because of dopamine's (DA) role in addiction, it is important to evaluate whether this subpopulation of neurons contributes to addiction-related phenotypes. Furthermore, the effects of gender on the relationship between Ucn 1 and tyrosine hydroxylase (TH) in pIII and alcohol preference in rats have not been previously assessed. Methods:, To address these issues, we compared 2 Sardinian alcohol-preferring sublines of rats, a population maintained at the Scripps Research Institute (Scr:sP) and a population maintained at University of Camerino,Marchigian Sardinian preferring rats (msP), to corresponding nonselectively bred Wistar rats of both sexes. Ucn 1- and TH-positive cells were detected on coronal midbrain sections from 6- to 8-week-old alcohol-naïve animals using brightfield and fluorescent immunohistochemistry. Ucn 1- and TH-positive cells in pIII were counted in the perioculomotor area, averaged across 2 to 3 sets, and binned into 3 bregma levels. Results:, Results demonstrated increased average counts of Ucn 1-positive cells in the middle bregma level in preferring male rats compared to Wistar controls and no difference in TH-positive cell counts in pIII. In addition, fluorescent double labeling revealed no colocalization of Ucn 1-positive and TH-positive neurons. Ucn 1 but not TH distribution was influenced by gender with female animals expressing more Ucn 1-positive cells than male animals in the peak bregma level. Conclusions:, These findings extend previous reports of increased Ucn 1-positive cell distribution in preferring lines of animals. They indicate that Ucn1 contributes to increased alcohol consumption across different species and that this contribution could be gender specific. The results also suggest that Ucn1 regulates positive reinforcing rather than aversive properties of alcohol and that these effects could be mediated by CRF2 receptors, independent of direct actions of DA. [source]

Reduction of Alcohol's Reinforcing and Motivational Properties by the Positive Allosteric Modulator of the GABAB Receptor, BHF177, in Alcohol-Preferring Rats

ALCOHOLISM, Issue 10 2009
Paola Maccioni
Background:, The positive allosteric modulators of the GABAB receptor, CGP7930 and GS39783, have been found to reduce alcohol self-administration in alcohol-preferring rats. The present study was designed to assess the effect of the newly synthesized positive allosteric modulator of the GABAB receptor, BHF177, on alcohol's reinforcing and motivational properties in selectively bred Sardinian alcohol-preferring (sP) rats. Methods:, sP rats were initially trained to respond on a lever [on a fixed ratio 4 (FR4) schedule of reinforcement] to orally self-administer alcohol (15%, v/v) or sucrose (1 to 3%, w/v) in daily 30-minute sessions. Once responding reached stable levels, rats were allocated to 2 different experiments: in the first experiment, rats were exposed to sessions with the FR4 schedule of reinforcement; in the second experiment, rats were exposed to sessions with a conventional progressive ratio (PR) schedule of reinforcement. In both experiments, the effect of BHF177 (0, 12.5, 25, and 50 mg/kg; i.g.) on responding for alcohol and sucrose (FR experiment: 1%, w/v; PR experiment: 3%, w/v) was determined. Results:, In the FR experiment, pretreatment with 25 and 50 mg/kg BHF177 produced a 30 and 45% reduction, respectively, in responding for alcohol. In the PR experiment, pretreatment with 50 mg/kg BHF177 resulted in a 35% reduction in breakpoint for alcohol (defined as the lowest response requirement not achieved by each rat and used as index of the motivational strength of alcohol). In both experiments, the effect of BHF177 on alcohol self-administration was specific, since responding for sucrose was unaltered by BHF177 pretreatment. Conclusions:, The present results extend to BHF177 the capacity of the 2 previously tested positive allosteric modulators of the GABAB receptor, CGP7930 and GS39783, to specifically suppress alcohol's reinforcing and motivational properties in alcohol-preferring rats. [source]

Association of Markers in the 3, Region of the GluR5 Kainate Receptor Subunit Gene to Alcohol Dependence

ALCOHOLISM, Issue 5 2009
Henry R. Kranzler
Background:, Glutamate neurotransmission plays an important role in a variety of alcohol-related phenomena, including alcohol self-administration by both animals and humans. Because the risk for alcohol dependence (AD) is genetically influenced, genes encoding glutamate receptors are candidates to contribute to the risk for AD. We examined the role of variation in the 3, region of GRIK1, the gene that encodes the GluR5 receptor subunit of the kainic acid glutamate receptor, on risk for AD. We focused specifically on this gene because topiramate, a glutamate modulator that binds to the GluR5 subunit, has shown robust efficacy in the treatment of AD. Methods:, We genotyped 7 single nucleotide polymorphisms (SNPs) in the 3,-half of GRIK1, which includes 3 differentially spliced exons, in a sample of EA control subjects (n = 507) and subjects with AD (n = 1,057). Results:, We found nominally significant evidence of association to AD for 3 SNPs (rs2832407 in intron 9, rs2186305 in intron 17, and rs2832387 in the 3,UTR). Empirical p -value estimation revealed that only rs2832407 was significantly associated to phenotype (p = 0.043). Discussion:, These findings provide support for the hypothesis that variation in the 3, portion of the gene encoding the GluR5 kainate receptor subunit contributes to the risk for AD. Further research is needed to ascertain whether this SNP is itself functional or whether the association reflects linkage disequilibrium with functional variation elsewhere in the gene and whether this SNP moderates topiramate's effects in the treatment of AD. [source]

Abstinence From Moderate Alcohol Self-Administration Alters Progenitor Cell Proliferation and Differentiation in Multiple Brain Regions of Male and Female P Rats

Gender and Age at Drinking Onset Affect Voluntary Alcohol Consumption but Neither the Alcohol Deprivation Effect nor the Response to Stress in Mice

ALCOHOLISM, Issue 12 2008
Sophie Tambour
Background:, Epidemiological studies suggest that initiation of alcohol drinking at an early age is associated with an increased risk of developing an alcohol use disorder later in life. Nevertheless, relatively few studies using animal models have investigated the relationship between age of onset of drinking and ethanol drinking patterns in adulthood. Besides age at drinking onset, other factors such as gender could also affect the pattern of development of alcohol consumption. In rodents, many studies have shown that females drink more than males. However, even if it is assumed that hormonal changes occurring at puberty could explain these differences, only one study performed in rats has investigated the emergence of sex-specific alcohol drinking patterns in adolescence and the transition from adolescence to adulthood. The aim of the present study was to compare the acquisition of voluntary alcohol consumption, relapse-like drinking (the Alcohol Deprivation Effect,ADE) and stress-induced alcohol drinking in male and female outbred mice that acquired alcohol consumption during adolescence or adulthood. Methods:, Separate groups of naïve female and male WSC-1 mice aged ± 28 days (adolescents) or ±70 days (adults) were given ad libitum access to water and 6% ethanol solution for 8 weeks (1st to 8th week) before undergoing a 2-week deprivation phase (9th and 10th week). After the deprivation period, 2-bottle preference testing (ethanol vs. water) resumed for 3 weeks (11th to 13th). During the 13th week, all animals were subjected to restraint stress for 2 consecutive days. Results:, Over the entire time course of the experiment, ethanol intake and preference increased in females (both adults and adolescents). Adolescent animals (both females and males) showed a transient increase in alcohol consumption and preference compared to adults. However, by the end of continuous alcohol exposure (when all mice were adults), ethanol intake was not affected by age at drinking onset. A deprivation phase was followed by a rise in ethanol intake (ADE) that was not affected by sex or age. Finally, stress did not alter alcohol self-administration either during or after its occurrence. Conclusions:, Emergence of greater alcohol consumption in adult females does not seem to be limited to a specific developmental period (i.e., puberty). Age of voluntary drinking onset (adolescence vs. adulthood) does not affect eventual alcohol intake in adult WSC-1 mice and does not modify the transient increase in ethanol consumption after alcohol deprivation. [source]

Environmental Cues, Alcohol Seeking, and Consumption in Baboons: Effects of Response Requirement and Duration of Alcohol Abstinence

Influence of Age at Drinking Onset on Long-Term Ethanol Self-Administration With Deprivation and Stress Phases

ALCOHOLISM, Issue 7 2005
Sören Siegmund
Background: Onset of alcohol use during adolescence has potentially long-lasting consequences, e.g., prospective alcohol dependence. To obtain new insight into the effects of early chronic ethanol consumption, we compared the drinking behavior of two adult male Wistar rat groups: one that initiated alcohol consumption during adolescence (adolescent group) and the other that initiated their drinking during adulthood (adult group) in a model of long-term alcohol self-administration. We investigated the magnitude of the effects of deprivation and stress on alcohol intake and the influence of these events on the alcohol drinking behavior across time. Methods: Heterogeneous Wistar rats aged 31 days (adolescents) and 71 days (adults) were given ad libitum access to water, as well as 5% and 20% ethanol solutions during an observation period of 30 wk. A deprivation phase of 14 days was instituted after eight wk of access to alcohol. After 16 and 26 wk of alcohol access, all animals were subjected for three consecutive days to forced swimming and electric foot shocks, respectively. Results: At the onset of drinking, adolescent animals consumed less alcohol and showed lower preference than adults. The deprivation phase was followed by increased intake of highly concentrated ethanol solution without appreciable differences between age groups. Repeated swim stress produced a slight increase in ethanol consumption in both animal groups; however, alcohol intake was not significantly different between groups, whereas the foot shock stress-induced increase in alcohol intake was significantly higher in the animal group that initiated alcohol consumption during adolescence. After swim stress, the drinking behavior of the adolescent group resembled that of the adult group. In particular, the adolescent group increased their preference for 20% ethanol solution for the remainder of the experiment. Conclusions: Age of voluntary alcohol drinking onset does not appear to be a strong predictor for prospective alcohol intake and relapse-like drinking behavior under the present experimental conditions. However, male Wistar rats that initiated alcohol consumption during adolescence seem to be more susceptible to acute stressor-specific effects in terms of alcohol consumption. [source]

Use of Genetic Analyses to Refine Phenotypes Related to Alcohol Tolerance and Dependence

ALCOHOLISM, Issue 2 2001
John C. Crabbe
Various explanations for the dependence on alcohol are attributed to the development of tolerance to some of alcohol's effects, alterations in sensitivity to its rewarding effects, and unknown pathologic consequences of repeated exposure. All these aspects of dependence have been modeled in laboratory rodents, and these studies have consistently shown a significant influence of genetics. Genetic mapping studies have identified the genomic location of the specific genes for some of these contributing phenotypes. In addition, studies have shown that some genes in mice seem to affect both alcohol self-administration and alcohol withdrawal severity: genetic predisposition to high levels of drinking covaries with genetic predisposition to low withdrawal severity, and vice versa. Finally, the role of genetic background on which genes are expressed is important, as are the specifics of the environment in which genetically defined animals are tested. Understanding dependence will require disentangling the multiple interactions of many contributing phenotypes, and genetic analyses are proving very helpful. However, rigorous understanding of both gene-gene and gene-environment interactions will be required to interpret genetic experiments clearly. [source]