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Rationale: A adenosine receptors (AARs) have been proposed to be involved in drug addiction; however, preclinical studies about the effects of AAR ligands on alcohol consumption have provided inconsistent results. Objectives: The present study evaluated the effect of intraperitoneal injections of the AAR antagonist ANR 94, and the AAR agonists CGS 21680 and VT 7 on voluntary drinking and operant self-administration of 10% ethanol in Marchigian Sardinian alcohol-preferring (msP) rats. Results: Voluntary ethanol drinking was increased by ANR 94 in acute and subchronic experiments, while it was reduced by AAR agonists. The effect of CGS 21680 was abolished by a low dose of ANR 94, confirming its mediation by AARs. Ethanol self-administration was reduced by CGS 21680 and VT 7, while ANR 94 slightly but significantly increased it. Blood alcohol levels were not modified by AAR agonists, indicating that their effect is not related to ethanol pharmacokinetics. The effect of VT 7 on ethanol drinking was behaviourally selective; ethanol and food intake were reduced, but water intake was increased, and total fluid intake was not different from that of controls. Moreover, VT 7 did not affect locomotor activity. CGS 21680 (0.1 mg/kg) did not modify total fluid intake, but 0.2 and 0.3 mg/kg reduced total fluid intake and locomotor activity. Conclusion: These results provide evidence that AAR agonists reduce ethanol consumption in msP rats, which represent an animal model of alcohol abuse related to stress, anxiety and depression. AARs may represent a potential target for treatment of alcohol abuse. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Relapse to alcohol use during abstinence or maladaptive eating habits during dieting is often provoked by stress. The anxiogenic drug yohimbine, which causes stress-like responses in humans and non-humans, reliably reinstates alcohol and food seeking in a rat relapse model. Yohimibine is a prototypical alpha-2 adrenoceptor antagonist, but results from studies on noradrenaline's role in yohimbine-induced reinstatement of drug and food seeking are inconclusive. Here, we further addressed this issue by studying the effect of the alpha-1 adrenoceptor antagonist prazosin and the alpha-2 adrenoceptor agonist guanfacine on yohimbine-induced reinstatement. Methods: In exp. 1, we trained rats to self-administer alcohol (12% w/ v, 1 h/day), and after extinction of alcohol-reinforced lever pressing, we tested prazosin's (0.5, 1.0, and 2.0 mg/kg, i.p.) or guanfacine's (0.125, 0.25, and 0.5 mg/kg, i.p.) effect on yohimbine (1.25 mg/kg, i.p.)-induced reinstatement; we also examined prazosin's effect on intermittent-footshock-stress-induced reinstatement. In exp. 2, we trained food-restricted rats to self-administer 45 mg food pellets and first examined prazosin's or guanfacine's effects on food-reinforced responding, and then, after extinction of lever presses, on yohimbine-induced reinstatement. Results: Prazosin (0.5-2.0 mg/kg) blocked yohimbine-induced reinstatement of food and alcohol seeking, as well as footshock-induced reinstatement of alcohol seeking. Guanfacine attenuated yohimbine-induced reinstatement of alcohol seeking at the highest dose (0.5 mg/kg), but its effect on yohimbine-induced reinstatement of food seeking was not significant. Neither prazosin nor guanfacine affected high-rate food-reinforced responding. Conclusions: Results demonstrate an important role of postsynaptic alpha-1 adrenoceptors in stress-induced reinstatement of alcohol and food seeking. [ABSTRACT FROM AUTHOR]

Abstract: Chronic ethanol consumption is able to modify emotional behaviour and cognition in humans. In particular, the effects exerted by alcohol may depend on doses, time and modalities of administration. In this study we investigated, in adult male rats, ethanol self-administration and preference patterns using a 3-bottle choice paradigm with water, 10% ethanol solution, and white wine (10%, v/v), along a four-week period. The influence of alcohol free-access on novelty-induced explorative behaviour in the open field, and on spatial learning and reference memory in the Morris water maze was also evaluated. Our results indicate that: (i) rats show a higher preference for alcohol, in the first two weeks of the paradigm, displaying a higher consumption of 10% ethanol solution than white wine; in the last two weeks, they reduce their alcoholic preference, drinking the same moderate amounts of the two alcoholic beverages; (ii) at the fourth week of the free-access paradigm rats show a high explorative behaviour in the central squares of the open field and an improvement in spatial information processing in the new-place learning task of the Morris water maze. In conclusion our data suggest that, interestingly, rats exposed to the free-access paradigm were able to self-regulate their alcoholic intake, and indicated that a moderate alcohol consumption was able to induce an increase in behavioural reactivity and an enhancement in spatial learning flexibility. [Copyright &y& Elsevier]

Abstract: Preclinical and clinical evidence suggest an association between alcoholism and the primary regulator of extracellular dopamine concentrations, the dopamine transporter (DAT). However, the nature of this association is unclear. We determined if 10 days of voluntary alcohol self-administration followed by withdrawal could directly alter DAT function, or if genetically mediated changes in DAT function and/or availability could influence vulnerability to alcohol abuse. Heterozygous (DAT+/−) and homozygous mutant (DAT−/−) and wild-type (DAT+/+) mice were allowed to consume 5% alcohol in a schedule-induced polydipsia (SIP) task. In vivo fixed potential amperometry in anesthetized mice was used to (1) identify functional characteristics of mesoaccumbens dopamine neurons related to genotype, including dopamine autoreceptor (DAR) sensitivity, DAT efficiency, and DAT capacity, (2) determine if any of these characteristics correlated with alcohol drinking observed in DAT+/+ and DAT+/− animals, and (3) determine if SIP-alcohol self-administration altered DAR sensitivity, DAT efficiency, and DAT capacity by comparing these characteristics in wild-type (DAT+/+) mice that were SIP-alcohol naïve, with those that had undergone SIP-alcohol testing. DAT−/− mice consumed significantly less alcohol during testing and this behavioral difference was related to significant differences in DAR sensitivity, DAT efficiency, and DAT capacity. These functional characteristics were correlated to varying degrees with g/kg alcohol consumption in DAT+/+ and DAT+/− mice. DAR sensitivity was consistently reduced and DAT efficiency was enhanced in SIP-alcohol–experienced DAT+/+ mice when compared with naïve animals. These results indicate that DAR sensitivity is reduced by SIP-alcohol consumption and that DAT efficiency is modified by genotype and SIP-alcohol exposure. DAT capacity appeared to be strictly associated with SIP-alcohol consumption. [Copyright &y& Elsevier]

Abstract: Clinical evidence often points to stress as a cause or an antecedent to the development of drinking problems. Yet, animal models of alcohol drinking have yielded inconsistent evidence for a direct contribution of stress, and many studies have shown that stress suppresses alcohol consumption. The aim of the present study was to examine alcohol reward in animals exposed to repeated, mild social stress, and to determine whether alcohol drinking changes as a function of the temporal parameters of alcohol access relative to the stressor. Male Long-Evans rats, trained to self-administer a 6% (wt/vol) alcohol solution using a sucrose-fading procedure, were exposed to five brief (5min) episodes of contact with an aggressive male. Full contact with the resident was limited to a single episode of defeat, whereas the following four encounters occurred with the subjects behind a protective wire mesh cage. Alcohol self-administration was measured 1 week prior to stress (baseline), on each day of stress exposure, and 1 week following stress. Separate groups of animals were randomly assigned to self-administer alcohol immediately prior, immediately following, or 2h following defeat stress. Stress preferentially increased alcohol drinking on stress-exposure days, and further elevated the amount consumed 1 week following stress. Temporal parameters of alcohol access relative to the stressor were found to be important. Average alcohol consumption was greatest for animals drinking 2h postdefeat, whereas animals drinking immediately prior to or following the stressor did not show a significant increase in alcohol consumption. Results suggest that mild social defeat stress is sufficient to elicit increases in alcohol consumption in nonpreferring strains of rodents, provided alcohol access occurs at an optimal time interval after the social defeat experience. [Copyright &y& Elsevier]

There is an extensive literature showing that the CB1 cannabinoid receptor antagonist rimonabant (SR141716) decreases alcohol consumption in animals, but little is known about its effects in human alcohol drinkers. In this study, 49 nontreatment-seeking heavy alcohol drinkers participated in a 3-week study. After a 1-week baseline, participants received either 20 mg/day of rimonabant or placebo for 2 weeks under double-blind conditions. During these 3 weeks, participants reported their daily alcohol consumption by telephone. Subsequently, they participated in an alcohol self-administration paradigm in which they received a priming dose of alcohol followed by the option of consuming either eight alcohol drinks or receiving $3.00 for each nonconsumed drink. Endocrine measures and self-rating scales were also obtained. Rimonabant did not change alcohol consumption during the 2 weeks of daily call-ins. Similarly, the drug did not change either alcohol self-administration or endocrine measures during the laboratory session. We conclude that the daily administration of 20 mg of rimonabant for 2 weeks has no effect on alcohol consumption in nontreatment-seeking heavy alcohol drinkers. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Environmental enrichment is known to greatly impact several rodent behaviors • Alcohol-preferring rats were kept under impoverished, standard, and enriched environment • Environmental enrichment slowed acquisition of operant alcohol self-administration • Environmental enrichment reduced the reinforcing and motivational properties of alcohol • The hedonic properties of environmental enrichment likely replaced those of alcohol Living in an enriched environment (EE) produces a notable impact on several rodent behaviors, including those motivated by drugs of abuse. This picture is somewhat less clear when referring to alcohol-motivated behaviors. With the intent of contributing to this research field with data from one of the few rat lines selectively bred for excessive alcohol consumption, the present study investigated the effect of EE on operant oral alcohol self-administration in Sardinian alcohol-preferring (sP) rats. Starting from Postnatal Day (PND) 21, male sP rats were kept under 3 different housing conditions: impoverished environment (IE; single housing in shoebox-like cages with no environmental enrichment); standard environment (SE; small colony cages with 3 rats and no environmental enrichment); EE (large colony cages with 6 rats and multiple elements of environmental enrichment, including 2 floors, ladders, maze, running wheels, and shelter). From PND 60, rats were exposed to different phases of shaping and training of alcohol self-administration. IE, SE, and EE rats were then compared under (i) fixed ratio (FR) 4 (FR4) schedule of alcohol reinforcement for 20 daily sessions and (ii) progressive ratio (PR) schedule of alcohol reinforcement in a final single session. Acquisition of the lever-responding task (shaping) was slower in EE than IE and SE rats, as the likely consequence of a "devaluation" of the novel stimuli provided by the operant chamber in comparison to those to which EE rats were continuously exposed in their homecage or an alteration, induced by EE, of the rat "emotionality" state when facing the novel environment represented by the operant chamber. Training of alcohol self-administration was slower in EE than IE rats, with SE rats displaying intermediate values. A similar ranking order (IE>SE>EE) was also observed in number of lever-responses for alcohol, amount of self-administered alcohol, and breakpoint for alcohol under FR4 and PR schedules of reinforcement. These data suggest that living in a complex environment reduced the reinforcing and motivational properties of alcohol in sP rats. These results are interpreted in terms of the reinforcing and motivational properties of the main components of EE (i.e., social interactions, physical activities, exploration, novelty) substituting, at least partially, for those of alcohol. [ABSTRACT FROM AUTHOR]

Alcohol-related cues may induce relapse to heavy alcohol drinking and promote molecular adaptations in discrete brain regions. An exact nature of these molecular alterations is still unknown. In the present study, rats trained to self-administer ethanol were tested for cue-induced reinstatement of ethanol seeking after 30 days of abstinence. Next, a detailed immunocytochemical analysis of c-Fos activation was performed within seven nuclei of the amygdala. In the second experiment, c-Fos activation after reinstatement of ethanol seeking induced by discrete cues was compared with the activation pattern of its putative partner (c-Jun) and regulators (extracellular signal-regulated kinases and c-Jun N-terminal kinases). Reexposure to ethanol-associated context cues (an extinction session) potentiated c-Fos expression within the basolateral and central amygdala. Repeated presentation of ethanol-associated discrete cues in an extinction/reinstatement session led to even stronger c-Fos activation in the latter nuclei. In the second experiment, reexposure to the ethanol-associated context and discrete cues activated both c-Jun and extracellular signal-regulated kinases (ERK1/2) in the basolateral amygdala. Our observations suggest that the basolateral and central amygdala may be specifically involved in alcohol-seeking behavior induced by discrete cues.Neuropsychopharmacology (2008) 33, 1835–1846; doi:10.1038/sj.npp.1301567; published online 12 September 2007 [ABSTRACT FROM AUTHOR]

For humans alcohol consumption often has devastating consequences. Wild mammals may also be behaviorally and physiologically challenged by alcohol in their food. Here, we provide a detailed account of chronic alcohol intake by mammals as part of a coevolved relationship with a plant. We discovered that seven mammalian species in a West Malaysian rainforest consume alcoholic nectar daily from flower buds of the bertam palm (Eugeissona tristis), which they pollinate. The 3.8% maximum alcohol concentration (mean: 0.6%; median: 0.5%) that we recorded is among the highest ever reported in a natural food. Nectar high in alcohol is facilitated by specialized flower buds that harbor a fermenting yeast community, including several species new to science. Pen-tailed treeshrews (Ptilocercus jowl,) frequently consume alcohol doses from the inflorescences that would intoxicate humans. Yet, the flower-visiting mammals showed no signs of intoxication. Analysis of an alcohol metabolite (ethyl glucuronide) in their hair yielded concentrations higher than those in humans with similarly high alcohol intake. The pentailed treeshrew is considered a living model for extinct mammals representing the stock from which all extinct and living treeshrews and primates radiated. Therefore, we hypothesize that moderate to high alcohol intake was present early on in the evolution of these closely related lineages. It is yet unclear to what extent treeshrews benefit from ingested alcohol per se and how they mitigate the risk of continuous high blood alcohol concentrations. [ABSTRACT FROM AUTHOR]

The purpose of this study was to test the hypothesis that activation of the dynorphin/kappa (κ)-opioid system has a role in the increased consumption of ethanol in dependent animals. The effects of three opioid receptor antagonists with different effects on opioid receptors, naltrexone, nalmefene, and nor-binaltorphimine (nor-BNI), were compared in their ability to decrease ethanol self-administration in nondependent and ethanol-dependent male Wistar rats. Nalmefene and naltrexone are both opioid receptor ligands with comparable molecular weights and pharmacokinetic profiles, but differing specificity for the three opioid receptor subtypes at low doses, while nor-BNI is a selective κ-opioid receptor antagonist. Dependence was induced in half the animals by subjecting them to a 4-week intermittent vapor exposure period in which animals were exposed to ethanol vapor for 14 h per day. Subsequent to dependence induction, nalmefene, naltrexone, and nor-BNI were tested for their ability to modulate self-administration of ethanol in vapor-exposed and control rats. The results indicated that both nalmefene and naltrexone induced a significant dose-dependent decrease in the number of lever presses for ethanol in both groups of animals. However, in ethanol-dependent animals, nalmefene was significantly more effective in suppressing ethanol intake than naltrexone. Nor-BNI selectively attenuated ethanol-dependent self-administration while leaving nondependent ethanol self-administration intact. Because naltrexone is primarily selective for the μ-opioid receptor, and nalmefene is primarily selective for the μ- and κ-opioid receptor subtypes, the fact that nalmefene demonstrates more suppression in dependent animals suggests that opioid systems distinct from the μ-regulated portion may be involved in the increased drinking seen during withdrawal in dependent animals. The results with nor-BNI confirm that κ-opioid receptor antagonism selectively decreases dependence-induced ethanol self-administration, which supports the hypothesis that dynorphin/κ-opioid systems are dysregulated in dependence and contribute to the increased drinking seen during acute withdrawal in dependent rats.Neuropsychopharmacology (2008) 33, 643–652; doi:10.1038/sj.npp.1301438; published online 2 May 2007 [ABSTRACT FROM AUTHOR]

Yohimbine is an alpha-2 adrenoreceptor antagonist that provokes stress- and anxiety-like responses in both humans and laboratory animals. In rats, yohimbine increases operant alcohol self-administration and reinstates alcohol seeking. In this study, we assess whether these effects of yohimbine are attenuated by systemic injections of the corticotrotropin-releasing factor 1 (CRF1) receptor antagonist antalarmin. In Exp. 1, we trained rats to lever press for alcohol solutions (12% w/ v, 1 h/day) over several weeks; during training, the response requirement was increased from a fixed-ratio-1 (FR-1) to a fixed-ratio-3 (FR-3) reinforcement schedule. We then tested the effect of antalarmin (10 or 20 mg/kg) on yohimbine (1.25 mg/kg)-induced increases in operant alcohol self-administration (FR-3 reinforcement schedule). Subsequently, we assessed the effect of antalarmin on yohimbine-induced increases in plasma corticosterone levels in the previously self-administering rats. In Exp. 2, we trained the rats to self-administer alcohol as in Exp. 1, and after extinction of the alcohol-reinforced lever responding over 13 days, we tested antalarmin’s effect on yohimbine-induced reinstatement of alcohol seeking. Yohimbine increased operant alcohol self-administration and reinstated alcohol seeking after extinction. These effects of yohimbine were attenuated by antalarmin. Antalarmin injections in the absence of yohimbine had no effect on either operant alcohol self-administration or extinction responding. Antalarmin had no effect on yohimbine-induced corticosterone release in alcohol-experienced rats. These results suggest that extrahypothalamic CRF1 receptors are involved in the effect of yohimbine on operant alcohol self-administration and on relapse to alcohol seeking and support the notion that CRF1 receptor antagonists should be considered in alcohol addiction treatment. [ABSTRACT FROM AUTHOR]

The positive allosteric modulator of the GABAB receptor, GS39783, has recently been found to suppress acquisition and maintenance of alcohol drinking behavior in selectively bred Sardinian alcohol-preferring (sP) rats exposed to the standard, homecage two-bottle “alcohol vs water” choice regimen. The present study was designed to extend the characterization of the “anti-alcohol” effects of GS39783 to oral self-administration of alcohol under an operant procedure. Two separate groups of male sP rats were trained to lever-press (on an FR4 schedule) to orally self-administer alcohol (15%, v/ v) or sucrose (0.3%, w/ v) in daily 30-min sessions. Once lever-pressing behavior reached stable levels, the effect of GS39783 (0, 25, 50, and 100 mg/kg, i.g.) on responding for alcohol and sucrose was determined. Pretreatment with GS39783 resulted in a significant, dose-dependent reduction in responding for alcohol; at the dose of 100 mg/kg GS39783, the number of lever responses for alcohol was reduced by approximately 50% in comparison to vehicle-treated rats. The effect of GS39783 on alcohol self-administration was specific, as responding for sucrose was completely unaffected by pretreatment with GS39783. These data demonstrate the capability of GS39783 to attenuate the reinforcing properties of alcohol in alcohol-preferring rats. These data constitute a further piece of experimental evidence in support of the hypothesized role for the GABAB receptor in the control of alcohol drinking and reinforcement. [ABSTRACT FROM AUTHOR]

The present study examined the effects of the acute intraperitoneal (i.p.) administration of the selective dopamine (DA) D3 receptor antagonist SB-277011A (10, 20 or 30 mg/kg i.p.) on the oral operant self-administration of alcohol in male C57BL/6N mice. These effects were compared with those of naltrexone (0.5, 1 and 2 mg/kg i.p.) and acamprosate (100, 200 and 400 mg/kg i.p.). Compared with vehicle, the acute administration of SB-277011A (10 or 20 mg/kg) did not significantly alter the operant self-administration of alcohol, whereas the 30 mg/kg dose significantly reduced alcohol intake (g/kg), the number of reinforcers, and the number of active lever presses. The oral self-administration of alcohol was not significantly altered by the acute administration of either naltrexone or acamprosate, compared with vehicle-treated mice. SB-277011A, naltrexone and acamprosate were also tested in a model of drug/cue-triggered reinstatement of alcohol-seeking behavior. In this model, neither naltrexone (2 mg/kg) nor acamprosate (400 mg/kg) prevented relapse to alcohol-seeking behavior. In contrast, SB-277011A significantly reduced reinstatement of alcohol seeking in a dose-dependent manner. Provided these results can be extrapolated to humans, they suggest that selective DA D3 receptor antagonists may be useful in the pharmacotherapeutic management of alcohol intake and prevention of relapse to alcohol-seeking behavior. [ABSTRACT FROM AUTHOR]

The authors used the sucrose-substitution procedure to train operant self-administration of a 10% alcohol solution in 8 Long-Evans rats. After they established stable responding, they began a 10-session baseline. A 10-session experimental phase followed the baseline phase. During the experimental phase, the authors placed a large glass marble in the center of the experimental chambers before self-administration sessions. The presence of the marble decreased the rats' responding and alcohol intake significantly. The authors discussed the results in terms of distraction and the effects of concurrently available reinforcers on alcohol self-administration. [ABSTRACT FROM AUTHOR]

Abstract: We have recently shown that the alcohol self-administration context can reinstate extinguished responding for alcohol when that extinction occurs in a different context [Burattini, C., Gill, T. M., Aicardi, G., & Janak, P. H. (2006)]. The ethanol self-administration context as a reinstatement cue: acute effects of naltrexone. Neuroscience, in press; Zironi, I., Burattini, C., Aicardi, G., & Janak, P. H. (2006). Context is a trigger for relapse to alcohol. Behav Brain Res 167, 150–155). Here, we test whether the C57BL/6 mice will also show context-induced reinstatement for alcohol, and whether presentation of an alcohol-associated cue will alter the observed responding. Male C57BL/6 mice were trained to lever press on a fixed ratio-3 schedule for a 10% ethanol solution in a context made distinctive using visual, tactile, and olfactory stimuli. Each ethanol delivery was paired with a compound tone-light stimulus. After training, extinction sessions were given in a distinct context, comprised of different visual, tactile, and olfactory stimuli; the compound cue and the alcohol were not available during these sessions. In Experiment 1, after response extinction, subjects were tested by placement into both the alcohol self-administration context and, on a subsequent test, by response-contingent presentation of the cue following placement into the alcohol self-administration context. In Experiment 2, after response extinction, subjects were tested in both of these conditions, with the addition of a test of the effects of response-contingent presentation of the cue in the extinction context. The results indicate that the alcohol self-administration context produces a mild increase in responding at the alcohol lever, and that presentation of the alcohol-associated cue in the alcohol context, but not the extinction context, strongly increases responding on the alcohol lever. These findings suggest that the power of an alcohol-associated cue can be modulated by the context. The observed effects of alcohol contexts and cues on alcohol-seeking behavior in the C57BL/6 mouse suggest that this reinstatement model may be useful for understanding the neurobiological and genetic mechanisms of relapse triggered by conditioned environmental stimuli. [Copyright &y& Elsevier]

Presents a study which characterized the effects of social defeat or a cue associated with the defeat experience on reinstatement of alcohol seeking in rats. Examination into the effect of unconditioned and conditioned social defeat on alcohol self-administration; Effects of peppermint odor cue on self-administration; Interpretation of the study findings.

Abstract: Recent studies have demonstrated that treatment with the γ-aminobutyric acid (GABAB) receptor agonist, baclofen, reduces alcohol intake in selectively bred Sardinian alcohol-preferring rats tested under the homecage two-bottle “alcohol versus water” choice regimen. This study was designed to investigate whether baclofen also reduces alcohol-reinforcing effects in Sardinian alcohol-preferring rats. To this aim, sP rats were trained to lever press for oral alcohol (15%, vol/vol) or sucrose (0.3%, wt/vol; included as alternative reinforcer to evaluate the specificity of baclofen effect on alcohol reinforcement) under a fixed ratio schedule of 4. Once steady levels of alcohol or sucrose self-administration behavior were established, the effects of acutely administered baclofen (0, 1.7, and 3mg/kg, intraperitoneal [ip]) and naloxone (0, 1, and 3mg/kg, ip; included as reference compound) on alcohol- or sucrose-reinforced responding were evaluated. Baclofen administration dose dependently, although not specifically, reduced alcohol-reinforced responding to an extent comparable to that of naloxone. Baclofen also produced a dose-dependent and specific delay in the onset of alcohol-reinforced responding, suggesting that it suppressed the rats'' motivation to start drinking alcohol. These data are discussed in terms of adding further support to the hypothesized involvement of the GABAB receptor in the neural system mediating alcohol reinforcement. These data are also in agreement with the results of recent preliminary clinical studies suggesting that baclofen may have therapeutic efficacy in the treatment of alcohol dependence. [Copyright &y& Elsevier]

Discusses a research on the role of alpha-2 adrenoceptors in stress-induced reinstatement of alcohol seeking and alcohol self-administration in rats. Effect of lofexidine and yohimbine on alcohol self-administration; Impact of stress on craving and relapse to alcohol and drugs; Investigation of the neuropharmacological basis of stress-induced alcohol.

Rationale. A growing number of studies suggest that γ-aminobutyric acid type-B (GABAB) receptor agonists reduce alcohol use and craving. Objectives. This study was designed to further clarify behavioral mechanism(s) by which GABAB agonists may decrease alcohol reinforcement. Methods. Male C57BL/6 J mice were trained to lever press on a concurrent schedule of ethanol (10% v/v) and water reinforcement during 16-h overnight sessions. Effects of the GABAB agonist baclofen (0–17 mg/kg, IP) or SKF 97541 (0–1 mg/kg, IP) were examined on parameters of self-administration. Subsequently, potential motor inhibition and interaction with ethanol-induced sedation by GABAB agonists was examined in ethanol naive and self-administering mice. Results. Baclofen (10 mg/kg) and SKF 97541 (0.3 mg/kg) reduced ethanol-reinforced responding. In a locomotor activity test, these doses of the GABAB agonists inhibited locomotion in the ethanol-experienced mice and in a group of ethanol-inexperienced mice; locomotor suppression was greater in the ethanol-inexperienced mice. These doses of the GABAB agonists also potentiated the sedative effects of ethanol (4 g/kg) and converted a nonsedative dose of ethanol (2 g/kg) into a fully sedative dose. GABAB agonist enhancement of the sedative effects of ethanol was less pronounced in ethanol self-administering mice, suggesting cross-tolerance at the low dose of ethanol. Conclusions. GABAB agonists decrease the reinforcing effects of ethanol at doses that inhibit locomotor activity and potentiate the sedative hypnotic effects of ethanol. These nonspecific effects of GABAB agonists were reduced in alcohol experienced mice, suggesting cross-tolerance to the inhibitory properties of GABAB positive modulation. These data question the safety of prescribing GABAB agonists to alcoholics since these drugs may potentiate ethanol’s sedative/hypnotic effects during relapse. [ABSTRACT FROM AUTHOR]

Rationale. Nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the opioid-like orphan receptor NOP, was shown to reduce home-cage ethanol consumption, ethanol-induced conditioned place preference and stress-induced reinstatement of alcohol-seeking behaviour. Objectives. The present study, using genetically selected Marchigian Sardinian alcohol-preferring (msP) rats, was designed to evaluate the effect of this opioid peptide on 10% ethanol and 10% sucrose self-administration, under a fixed-ratio 1 (FR 1) or a progressive-ratio (PR) schedule of reinforcement. Furthermore, using an experimental model of relapse in which rats were trained to lever press for ethanol in the presence of the discriminative stimulus of an orange odour (S[sup +]) and a 1-s cue light (CS[sup +]) or for water in the presence of anise odour (S[sup -]) and 1-s white noise (CS[sup -]), the effect of N/oFQ on cue-induced reinstatement of extinguished ethanol responding was investigated. Results. Sub-chronic (6 days) intracerebroventricular (i.c.v.) injection of 0.5 μg or 1.0 μg N/OFQ per rat significantly reduced alcohol self-administration under both the FR 1 and PR schedules of reinforcement. Conversely, i.c.v. administration of 0.5, 1.0 or 4.0 μg of the peptide per rat did not affect sucrose self-administration. In addition, i.c.v. N/OFQ (1.0–2.0 μg per rat) significantly inhibited the reinstatement of extinguished ethanol responding under an S[sup +]/CS[sup +] condition, whereas lever pressing under S[sup -]/CS[sup -] was not altered. Conclusions. The present study demonstrates that the reinforcing effects of ethanol are markedly blunted by activation of the opioidergic N/OFQ receptor system. Moreover, the data provide evidence of the efficacy of N/OFQ to prevent reinstatement of ethanol-seeking behaviour elicited by environmental conditioned stimuli. [ABSTRACT FROM AUTHOR]

Background: Alcohol and nicotine, in the form of tobacco, are commonly co-abused. Nicotinic receptors also have been implicated in alcohol action. We designed the present study to examine the possible involvement of nicotinic receptors in alcohol self-administration. Methods and Results: Pretreatment with lower doses (0.1-0.4 mg/kg) of nicotine, administered acutely or chronically, did not affect alcohol consumption, whereas a higher dose (0.8 mg/kg) initially suppressed alcohol consumption but stimulated alcohol consumption on repeated treatment. We observed the same pattern of nicotine effects on alcohol self-administration using an operant procedure. A dose of 0.8 mg/kg of nicotine initially suppressed operant responding for alcohol. Such suppression of alcohol self-administration was more pronounced during the first 20 min of the 60 min operant session. Responding for alcohol in the nicotine treated group, however, was significantly increased above the saline treated group by the 5th day of treatment. Mecamylamine, a noncompetitive nicotinic receptor antagonist, reduced alcohol consumption, whereas dihydro-β-erythroidine (DHβE), a competitive nicotinic receptor antagonist, did not modify alcohol consumption. Conclusions: The stimulation of alcohol intake induced by nicotine treatment and the suppression of alcohol intake induced by mecamylamine provide evidence for the involvement of nicotinic receptors in alcohol consumption and/or self-administration. The failure of DHβE to reduce alcohol consumption, however, suggests that ethanol-nicotine interaction is mediated by other nicotinic receptor subtypes rather than α4β2 receptor subtype, or that mecamylamine acts through a nonnicotinic mechanism. [ABSTRACT FROM AUTHOR]

Introduction: Cannabidiol (CBD) is a major cannabinoid extracted from Cannabis sativa with no abuse potential. Data from recent rodent studies suggest that amelioration of alcohol-motivated behaviors may be one of the numerous pharmacological effects of CBD. This study was designed to contribute to this research, assessing the effect of CBD on operant oral alcohol self-administration in selectively bred Sardinian alcohol-preferring (sP) rats, a validated animal model of excessive alcohol consumption. In addition, this study investigated the effect of CBD on operant self-administration of a highly palatable chocolate solution in Wistar rats. Materials and Methods: Male sP rats were trained to lever respond for alcohol (15% v/v) under the fixed ratio 4 (FR4) schedule of reinforcement. Once lever responding had stabilized, rats were exposed to test sessions under the FR4 and progressive ratio (PR) schedules of reinforcement. Test sessions were preceded by acute treatment with CBD (0, 6.25, 12.5, and 25 mg/kg or 0, 25, 50, and 100 mg/kg, i.p.; each dose range was tested in an independent experiment). Male Wistar rats were trained to lever respond for a chocolate solution (5% w/v chocolate powder) under the FR10 schedule of reinforcement. Once lever responding had stabilized, rats were exposed to test sessions under the same schedule. Test sessions were preceded by acute treatment with CBD (0, 6.25, 12.5, and 25 mg/kg or 0, 25, 50, and 100 mg/kg, i.p., in two independent experiments). Results: Under the FR schedule, treatment with doses of CBD ≥12.5 mg/kg markedly reduced lever responding for alcohol and amount of self-administered alcohol. Under the PR schedule, treatment with CBD produced a slight tendency toward a decrease in lever responding and breakpoint for alcohol. Finally, no dose of CBD affected lever responding for the chocolate solution and amount of self-administered chocolate solution. Discussion: These results extend previous data on CBD ability to affect alcohol-motivated behaviors to an animal model of genetically-determined proclivity to high alcohol consumption. Because of the predictive validity of sP rats, these results may be of relevance in view of possible future studies testing CBD in patients affected by alcohol use disorder.

Many of the behavioral symptoms that define alcohol use disorder (AUD) are thought to be mediated by amplified glutamatergic activity. As a result, previous preclinical studies have investigated glutamate receptor inhibition as a potential pharmacotherapy for AUD, particularly the metabotropic glutamate receptor 5 (mGlu5). In rodents, mGlu5 negative allosteric modulators (NAMs) have been shown to decrease alcohol self-administration. However, their effect on non-human primates has not previously been explored. To bridge this gap, the effects of mGlu5 NAM pretreatment on sweetened alcohol (8% w/v in diluted KoolAid) self-administration in female baboons were evaluated. Two different mGlu5 NAMs were tested: 1) 3-2((-Methyl-4-thiazolyl) ethynyl) pyridine (MTEP) which was administered at a dose of 2 mg/kg IM; and 2) auglurant (N -(5-fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide), a newly developed NAM, which was tested under two different routes (0.001, 0.01, 0.03, 0.1 mg/kg IM and 0.1, 0.3, 1.0 mg/kg PO). MTEP decreased both fixed ratio and progressive ratio responding for sweetened alcohol. Auglurant, administered IM, decreased alcohol self-administration at doses that did not affect self-administration of an alcohol-free sweet liquid reward (0.01 to 0.1 mg/kg). Oral administration of auglurant was not effective in decreasing alcohol self-administration. Our results extend positive findings from rodent studies on mGlu5 regulation of alcohol drinking to female baboons and further strengthen the rationale for targeting mGlu5 in clinical trials for AUD. • Female baboons were trained to self-administer high rates of sweetened alcohol (1.7-3.2 g/kg EtOH per day). • The mGlu5 negative allosteric modulator (NAM) MTEP reduced FR and PR responding for sweetened alcohol. • A newly developed mGlu5 NAM, auglurant, dose dependently and selectively reduced FR and PR responding for alcohol. • Oral administration of auglurant did not affect sweetened alcohol self-administration. [ABSTRACT FROM AUTHOR]

The aim of the present study was to determine whether reduction of dopamine (DA) innervation to the nucleus accumbens (ACB) alters the maintenance and/or acquisition of ethanol drinking in female alcohol-preferring P rats. Compared with sham-lesioned animals, bilateral microinjections of 6-OHDA (12 μg/2.4 μl/site) into the ACB did not alter the consumption of 10% ethanol in rats that had prior experience of ethanol drinking, with both sham- and 6-OHDA-lesioned groups recovering to presurgical consumption levels at similar rates. On the other hand, the identical lesion procedure disrupted the acquisition of ethanol intake in rats with no ethanol-drinking experience prior to the lesions. A sham-lesioned group attained an ethanol intake of approximately 7 g/kg/day in 1 week, which was maintained over the following 2-week period, while the ethanol intake of the 6-OHDA-lesioned group was approximately 60% lower after 1 week and 30% lower at the end of 3 weeks. DA content of the ACB was 60% lower in both groups of the 6-OHDA-treated rats compared with the controls. The results suggest that different neural mechanisms may underlie the acquisition and maintenance of ethanol drinking behavior; the ACB DA system appears to play an important role in the acquisition of ethanol drinking. [ABSTRACT FROM AUTHOR]

This study was performed to examine ethanol self-administration in rats bred for different sensitivities to the sedative effects of alcohol [the Colorado High Alcohol Sensitive (HAS) and Low Alcohol Sensitive (LAS) rats]. Four rats from each replicate line of the HAS and LAS rats ( n= 16) were obtained from the University of Colorado, and initiation to self-administer ethanol by the sucrose-substitution procedure was attempted. Before the initiation procedure was conducted, home-cage ethanol intake and preference ratio did not differ between LAS and HAS rats. During the initiation procedure, the LAS rats came to self-administer 10% ethanol (v/v) at similar levels as outbred Wistar rats initiated with the same procedure (˜0.4 g/kg/ session). The HAS rats, however, failed to initiate (˜0.08 g/kg/session after completing the sucrose-substitution procedure) and lever pressing was reduced even more in the HAS rats when the ethanol concentration presented was >10% (v/v). Three of the eight HAS rats stopped lever pressing completely when the ethanol concentration was raised to 15%. After initiation, home-cage preference ratio differed significantly between the LAS and HAS rats (LAS > HAS, p < 0.03). That the LAS rats did not consume greater amounts of ethanol compared with outbred Long-Evans or Wistar rats is contrary to our hypothesis, based on recent human data suggesting that a lower sensitivity to ethanol could result in increased alcohol intake. The finding that the HAS rats could not be initiated, while selectively bred ethanol nonpreferring rats can, is also contrary to our hypothesis. Further studies related to ethanol self-administration with the HAS line could provide important information related to the genetics of alcohol nonacceptance. [ABSTRACT FROM AUTHOR]

Rats, from the alcohol preferring (P) line, were placed in operant chambers in which food pellets, water, and 10% ethanol (v/v) were available continuously for 23 hr/day. During Experiment 1, the effects of changing ethanol concentration and response requirement for ethanol were examined. Ten percent and 20% ethanol (v/v) were available on two fixed ratio (FR) schedules, FR 1 and FR 4, for 2 weeks each. During Experiment 2, the effects of increasing the response requirement for ethanol were investigated. Starting with FR 4, the FR requirement for ethanol doubled during 2-week intervals until FR 32 was in effect. For the final phase of these studies, water was placed in the dipper for 1 week followed by a return to 10% ethanol in the dipper. The results from Experiment 1 indicated that when the FR requirement was decreased from FR 4 to FR 1, ethanol-reinforced responding decreased but total daily intake increased. Lowering the FR requirement did not affect the number of ethanol bouts per day but bout size increased. Ethanol concentration had no effect on bout size but the number of bouts per day decreased when the concentration was increased to 20%. Since bout size was unchanged by increasing the ethanol concentration, intake per bout increased at 20% ethanol. The results from Experiment 2 indicated that increasing the response requirement for ethanol decreases ethanol intake. When water was placed in the dipper, responding decreased to the lowest levels observed in the experiment. When ethanol was returned to the dipper, responding returned to baseline levels. Overall, the results indicate that while P rats may consume more ethanol than other lines of rats, their behavior can be modified by environmental variables in a manner somewhat similar to heterogeneous nonselected Long-Evans rats. [ABSTRACT FROM AUTHOR]

Rats were trained to lick at a drinking tube containing 5% ethanol to obtain access to a 0.1-ml dipper containing 20% sucrose. Following 20 of these drinking sessions, a lever press response was shaped and maintained with ethanol presentation in the dipper. This induction procedure resulted in rats responding on a FR 8 schedule of reinforcement to receive 40% (v/v) ethanol. Ethanol intakes over 0.5 g/kg in 30 min were obtained when ethanol concentrations over 10% were available. These intakes frequently resulted in blood ethanol levels over 100 mg ethanol/dl blood. This contingent sucrose induction procedure did not use food deprivation at any time. It is suggested that this procedure can be used to investigate the processes involved with the initiation of ethanol as a reinforcer independent of food restriction procedures. [ABSTRACT FROM AUTHOR]

Alcoholism is a chronically relapsing disorder characterized by high alcohol intake and a negative emotional state during abstinence, which contributes to excessive drinking and susceptibility to relapse. Stress, dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and alterations in glucocorticoid receptor (GR) function have been linked to transition from recreational consumption to alcohol use disorder (AUD). Here, we investigated the effect of pharmacological antagonisms of GR on alcohol self-administration (SA) using male and female Wistar and Marchigian Sardinian alcohol-preferring (msP) rats, a rodent line genetically selected for excessive alcohol drinking and highly sensitive to stress. Animals were trained to self-administer 10% (v/v) alcohol. Once a stable alcohol SA baseline was reached, we tested the effect of the GR antagonists mifepristone (0.0, 10, 30 and 60 mg/kg; i.p.) and CORT113176 (0.0, 10, 30 and 60 mg/kg) on alcohol SA. To evaluate whether the effects of the two compounds were specific for alcohol, the two drugs were tested on a similar saccharin SA regimen. Finally, basal blood corticosterone (CORT) levels before and after alcohol SA were determined. Systemic injection with mifepristone dose-dependently reduced alcohol SA in male and female Wistars but not in msPs. Administration of CORT113176 decreased alcohol SA in male and female Wistars as well as in female msPs but not in male msP rats. At the highest dose, mifepristone also reduced saccharin SA in male Wistars and female msPs, suggesting the occurrence of some nonspecific effects at 60 mg/kg of the drug. Similarly, the highest dose of CORT113176 (60 mg/kg) decreased saccharin intake in male Wistars. Analysis of CORT levels revealed that females of both rat lines had higher blood levels of CORT compared to males. Alcohol consumption reduced CORT in females but not in males. Overall, these findings indicate that selective blockade of GR selectively reduces alcohol SA, and genetically selected msP rats are less sensitive to this pharmacological manipulation compared to heterogeneous Wistars. Moreover, results suggest sex differences in response to GR antagonism and the ability of alcohol to regulate GR transmission. [ABSTRACT FROM AUTHOR]

Drug addiction is a chronic mental disorder characterized by frequent relapses. Contextual cues associated with drug use to play a critical causal role in drug-seeking behavior. The hippocampus has been implicated in encoding drug associative memories. Here we examine whether the dorsal hippocampus mediates context-induced reinstatement of alcohol-seeking. Male Long-Evans rats were trained to self-administer alcohol in Context A. Alcohol self-administration was extinguished in a distinct context (Context B). On the test day, animals were re-exposed to the alcohol Context A or the extinction Context B. Next, to assess a causal role for the dorsal hippocampus in context-induced alcohol-seeking, on the test day, we injected cobalt chloride (CoCl2; a nonselective synapse inhibitor) or vehicle into the dorsal hippocampus, and 15 min later, rats were tested by re-exposing them to the drug-associated context. The re-exposure to the alcohol-associated Context A reinstated alcohol seeking and increased Fos-positive cells in the dorsal hippocampus neurons (CA1, CA3, and Dentate Gyrus). Pharmacological inactivation with cobalt chloride of the dorsal hippocampus attenuated the reinstatement of alcohol-seeking. Our data suggest that the dorsal hippocampus may be involved in context-induced alcohol-seeking behavior. [ABSTRACT FROM AUTHOR]

Lead (Pb) is a neurotoxic heavy metal pollutant. Despite the efforts to reduce Pb environmental exposure and to prevent Pb poisoning, exposure in human populations persists. Studies of adults with history of childhood lead exposure have consistently demonstrated cognitive impairments that have been associated with sustained glutamate signaling. Additionally, some clinical studies have also found correlations between Pb exposure and increased proclivity to drug addiction. Thus, here we sought to investigate if developmental Pb exposure can increase propensity to alcohol consumption and relapse using an alcohol self-administration paradigm. Because Pb exposure is associated with increased glutamatergic tone, we also studied the effects on the expression of synaptic and non-synaptic glutamate transporters in brain regions associated with drug addiction such as the nucleus accumbens (NAc), dorsomedial striatum (DMS), dorsolateral striatum (DLS), and medial prefrontal cortex (mPFC). We found that while developmental Pb exposure did not increase risk for alcohol self-administration, it did play a role in relapsing to alcohol. The effects were associated with differential expression of the glutamate transporter 1 (GLT1) and the glutamate/cystine antiporter (xCT). In the NAc and DLS the expression of GLT1 was found to be significantly reduced, while no changes were found in DMS or mPFC. Contrastingly, xCT was found to be upregulated in NAc but downregulated in DLS, with no changes in DMS or mPFC. Our data suggest that lead exposure is involved in relapse to alcohol seeking, an effect that could be associated with downregulation of GLT1 and xCT in the DLS. • Developmental Pb exposure does not increase alcohol self-administration. • Low-level Pb exposure increase the risk of relapse to alcohol seeking. • Decreased expression of GLT1 and xCT glutamate transporters in dorsolateral striatum after relapsing to alcohol seeking. [ABSTRACT FROM AUTHOR]

Ultrasonic vocalizations (USVs) are well-established markers of motivational and emotional status. Recent work from our lab has provided novel evidence for a role of USVs in models of ethanol (EtOH) use. For instance, USV acoustic characteristics can be used to accurately discriminate between rats selectively bred for high EtOH intake (e.g., alcohol-preferring (P) and high-alcohol-drinking (HAD)) versus EtOH-avoiding (e.g., alcohol-non-preferring (NP) and low-alcohol-drinking (LAD)) strains, as well as differentiate between male and female rats. In the present study we sought to explore the effect of age and alcohol availability on spontaneously emitted 50–55 kHz frequency modulated (FM) and 22–28 kHz USVs in adult, male Long–Evans rats. With the hypothesis that age and alcohol experience influence spontaneous USV emissions, we examined USV data collected across a 24-week intermittent EtOH access experiment in male Long–Evans rats. USV counts and acoustic characteristic (i.e., mean frequency, duration, bandwidth and power) data revealed distinct age-dependent phenotypes in both 50–55 kHz FM and 22–28 kHz USV transmission patterns that were modulated by EtOH exposure. These results highlight the influence of age and EtOH experience on the unique emotional phenotypes of male Long–Evans rats. [ABSTRACT FROM AUTHOR]

Alcohol consumption is often assessed over weeks to months, but few attempts have been made to characterize alcohol consumption rates at the level of an individual drinking session. Here, we aimed to compare the rate of alcohol consumption in social drinkers at high risk for alcohol use disorder (AUD) and heavy drinkers. One hundred and sixty social drinkers and 48 heavy drinkers participated in an alcohol self‐administration study. Social drinkers were classified as low risk or high risk for AUD based on sex, impulsivity, and family history of alcoholism. Participants received a priming dose of intravenous alcohol to assess alcohol‐induced craving and completed a 125‐minute intravenous alcohol self‐administration session to assess rate of achieving a binge‐level exposure (blood alcohol concentration greater than or equal to 80 mg%). There were no differences between rates of binging in high‐risk and heavy drinkers (hazard ratio = 0.87; 95% CI, 0.48‐1.56). Heavy drinkers reported higher levels of craving than high‐risk and low‐risk drinkers at baseline. However, following a priming dose of alcohol, there were no longer differences in craving between high‐risk and heavy drinkers. These results indicate that high‐risk social drinkers demonstrate binging behavior that is similar to heavy drinkers, which may be driven by alcohol‐induced craving. Prospective studies are needed to elucidate whether these patterns of craving and consumption in high‐risk social drinkers are predictive of future AUD. [ABSTRACT FROM AUTHOR]

Alcohol consumption is often assessed over weeks to months, but few attempts have been made to characterize alcohol consumption rates at the level of an individual drinking session. Here, we aimed to compare the rate of alcohol consumption in social drinkers at high risk for alcohol use disorder (AUD) and heavy drinkers. One hundred and sixty social drinkers and 48 heavy drinkers participated in an alcohol self-administration study. Social drinkers were classified as low risk or high risk for AUD based on sex, impulsivity, and family history of alcoholism. Participants received a priming dose of intravenous alcohol to assess alcohol-induced craving and completed a 125-minute intravenous alcohol self-administration session to assess rate of achieving a binge-level exposure (blood alcohol concentration greater than or equal to 80 mg%). There were no differences between rates of binging in high-risk and heavy drinkers (hazard ratio = 0.87; 95% CI, 0.48-1.56). Heavy drinkers reported higher levels of craving than high-risk and low-risk drinkers at baseline. However, following a priming dose of alcohol, there were no longer differences in craving between high-risk and heavy drinkers. These results indicate that high-risk social drinkers demonstrate binging behavior that is similar to heavy drinkers, which may be driven by alcohol-induced craving. Prospective studies are needed to elucidate whether these patterns of craving and consumption in high-risk social drinkers are predictive of future AUD. [ABSTRACT FROM AUTHOR]

Background: Peer interactions can have important effects on alcohol-drinking levels, in some cases increasing use, and in other cases preventing it. In a previous study, we have established the prairie vole as a model animal for the effects of social relationships on alcohol intake and have observed a correlation of alcohol intake between individual voles housed together as pairs. Here, we investigated this correlated drinking behavior, hypothesizing that 1 animal alters its alcohol intake to match the drinking of its partner., Methods: Adult prairie voles were tested for baseline drinking levels with continuous access to 10% alcohol and water for 4 days. In Experiment 1, high alcohol drinkers (>9 g/kg/d) were paired with low alcohol drinkers (<5 g/kg/d) of the same sex on either side of a mesh divider for 4 days with continuous access to the same 2-bottle choice test. In Experiment 2, high drinkers were paired with high drinkers and low drinkers paired with low drinkers. In both experiments, animals were again separated following pairing, and drinking was retested in isolation. In Experiment 3, alcohol-naïve animals were tested for saccharin consumption (0.05%) first in isolation and then in high saccharin drinkers paired with low saccharin drinkers, and then in another isolation period., Results: In Experiment 1, high drinkers paired with low drinkers significantly decreased their alcohol intake and preference from baseline drinking in isolation, and drinking levels remained significantly lower during isolation following pairing. Interestingly, there was variability between pairs in whether the high drinker decreased or the low drinker increased intake. In Experiment 2, high drinkers paired with high drinkers did not significantly change their intake level or preference, nor did low drinkers paired with low drinkers, and no changes occurred during the subsequent isolation. In Experiment 3, there was no change in saccharin intake or preference when high drinkers were paired with high drinkers or low paired with low, or in the subsequent isolation., Conclusions: Alcohol drinking of prairie voles can be altered under social conditions, such that 1 animal changes its alcohol intake to more closely match the intake of the other animal, helping to explain previous findings of correlated alcohol drinking. The effect does not extend to saccharin, a naturally rewarding sweet substance. This behavior can be used to model the peer pressure that can often affect alcohol intake in humans., (Copyright © 2011 by the Research Society on Alcoholism.)