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G F Koob

Publications and source records attributed to G F Koob.

At least 73 records · Page 4Linked to original sources
PubMed1999

Cellular responses of nucleus accumbens neurons to opiate-seeking behavior: I. Sustained responding during heroin self-administration.

The nucleus accumbens (NAcc) has been hypothesized to be a critical component of the circuit mediating opiate-seeking behaviors. To further explore the electrophysiological correlates of opiate-seeking behavior, we recorded neurons in the NAcc and in the medial prefrontal cortex (mPFC) of rats trained to self-administer heroin for at least 2 weeks. Rats were trained to lever press (FR-1 schedule) for an intravenous (i.v.) infusion of heroin (0.06 mg/kg/injection) in an operant chamber. Spontaneous single unit activity in the NAcc and the mPFC was then recorded while animals were allowed to self-administer heroin. Our data suggest that about 20% (8/42) of the NAcc neurons studied exhibited an inhibitory response immediately after heroin self-administration. However, most of the NAcc neurons studied (76%; 32/42) were not affected during heroin self-administration. In contrast, noncontingent injection of a similar dose of heroin (0.06 mg/kg/injection) had no effect on NAcc spontaneous activity (0/6). On the other hand, passive administration of higher doses of heroin (0.2-0.6/mg/kg/injection) markedly suppressed the firing rate in 46% (6/13) of the neurons studied. These effects of heroin on NAcc activity were antagonized by systemic administration ofnaloxone (4-6 mg/kg, i.v.). Studies characterizing the responses of mPFC neurons during heroin self-administration showed that 40% (2/5) of the neurons tested exhibited an inhibitory effect immediately after heroin self-administration. These data suggest that in animals well-trained to self-administer heroin, only a small number (20%) of the NAcc neurons studied responded to heroin self-administration. Further research is necessary to determine whether these responses are a function of the opiate-seeking state of the animal and the mechanism(s) responsible for these effects of heroin.

Animals↗
PubMed1999

Increased sensitivity to the locomotor depressant effect of a dopamine receptor antagonist during cocaine withdrawal in the rat.

The effect of a dopamine receptor antagonist on locomotor activity was examined during withdrawal from either self-administered or experimenter-administered cocaine. In the self-administration experiment, the locomotor response to a challenge injection of cis-flupenthixol was assessed in photocell cages at 4 h after the cessation of a 12-h cocaine self-administration session. Rats which had self-administered cocaine, and were challenged with cis-flupenthixol (0.05 mg/kg), were found to be hypoactive relative to controls. In the experimenter-administered cocaine experiment, animals were given eight IP injections of 15 mg/kg cocaine over a 9.5-h period, for a total of 120 mg/kg. At 4, 8, and 24 h (tested in three separate groups of rats) after cessation of the eight injections, the locomotor response to a challenge injection of saline or cis-flupenthixol was tested. Cocaine-treated animals displayed a dose-dependent, heightened sensitivity to the locomotor depressant effects of 0.05 mg/kg and 0.2 mg/kg cis-flupenthixol 4 h post-cocaine, whereas they did not show increased sensitivity to 0.05 mg/kg cis-flupenthixol 8 or 24 h post-cocaine. However, cocaine-treated animals displayed a mild hypoactivity 8 h post-cocaine. In a separate group of animals, a dose-response experiment was performed which indicated that a dose of cis-flupenthixol as high as 0.2 mg/kg was required to produce locomotor depression in cocaine-naive rats. The results of this study support clinical observations of dopamine antagonist-precipitated motor dysfunction in abstinent cocaine abusers, and lend further support to the hypothesis that alterations in dopaminergic neurotransmission consequent to prolonged cocaine exposure are partly responsible for some of the symptoms of cocaine withdrawal.

Analysis of Variance↗
PubMed1999

RU 24969, a 5-HT1A/1B agonist, elevates brain stimulation reward thresholds: an effect reversed by GR 127935, a 5-HT1B/1D antagonist.

Recent studies suggest that serotonergic neurotransmission through the serotonin-1B (5-HT1B) receptor is involved in reward processes. The purpose of the present studies was to investigate the effects of 5-HT(1B) receptor activation and antagonism on intracranial self-stimulation (ICSS) reward using a current-threshold ICSS task. Male Wistar rats were prepared with bipolar electrodes in the lateral hypothalamus. When stable baseline thresholds were established, the effects of the mixed 5-HT(1A)/1B receptor agonist, RU 24969 (0-1 mg/kg, SC), on ICSS behavior were assessed. Administration of this compound elevated ICSS thresholds without affecting response latencies, a measure of general motoric activity. The 5-HT(1B/1D) receptor antagonist, GR 127935 (0-10 mg/kg, SC), had no significant effect on ICSS behavior. However, pretreatment with an intermediate dose of GR 127935 (3 mg/kg), which was previously without effect on ICSS behavior, reversed the threshold-elevating effects of RU 24969 (1 mg/kg), suggesting the involvement of the 5-HT1B receptor in this effect of RU 24969 administration. Furthermore, pretreatment with RU 24969 (0.3 and 0.6 mg/kg), prior to 10 mg/kg cocaine hydrochloride, dose-dependently attenuated the threshold-reducing effects of cocaine. This result is interpreted as two opposing drug effects canceling each other out rather than a specific pharmacological antagonism. In conclusion, the results suggest that activation of 5-HT(1B) receptors reduces brain stimulation reward.

Animals↗
PubMed1999

Heroin self-administration in dependent Wistar rats: increased sensitivity to naloxone.

RATIONALE: Non-dependent and dependent opiate users appear to be driven by two distinct motivational factors: the primary reinforcing properties of the drug, and the negative reinforcing effects associated with relieving the negative affective component of opiate withdrawal in the dependent state. OBJECTIVE: To investigate the motivational significance of opioid dependence on heroin self-administration (HSA) in rodents. METHODS: Rats were trained to self-administer heroin intravenously (0.06 mg/kg per infusion; FRI), and opiate dependence was induced by subcutaneous implantation of two morphine (75 mg base) pellets. Rats in a non-dependent control group received placebo pellets. Three days after pellet implantation, HSA was resumed in daily 3-h sessions until baseline criteria were met and testing was conducted with subcutaneous injections of vehicle or naloxone (0, 0.003, 0.01, 0.03 mg/kg) 115 min into the session. RESULTS: Morphine-dependent rats significantly increased HSA upon 0.01 mg/kg naloxone treatment, but decreased response rates at 0.03 mg/kg. Placebo pellet-implanted rats increased heroin intake at the 0.01 and 0.03 mg/kg doses. In a second experiment, the HSA session was shortened to 1 h and the training dose reduced to 0.03 mg/kg per infusion in new groups of animals. HSA in placebo pellet-implanted rats was increased only following the highest dose of the antagonist, while dependent rats were still affected by naloxone doses of 0.003-0.03 mg/kg. When subjected to a progressive-ratio schedule (experiment 3), breaking point values in dependent animals were 198% above baseline. CONCLUSIONS: The present study supports the hypothesis that dependence-induction by morphine-pellet implant in rats resulted in increased sensitivity to very small naloxone doses, as measured by changes in HSA. Taken together, these data suggest that opiate dependence, as measured by changes in sensitivity to naloxone, is a continuum which can contribute to the motivational state of drug-seeking.

Animals↗
PubMed1999

Corticotropin-releasing factor antagonist attenuates the "anxiogenic-like" effect in the defensive burying paradigm but not in the elevated plus-maze following chronic cocaine in rats.

RATIONALE: Chronic cocaine abuse is associated with the development of anxiogenic states in humans. Corticotropin-releasing factor (CRF) is an endogenous neurotropic factor well known to modulate stress responses. It has been postulated that CRF is involved in the neurobiological mechanisms underlying the anxiety and/or stress responses associated with removal of cocaine after chronic administration. OBJECTIVE: The present study investigated the role of endogenous CRF in mediating the "anxiety-like" effect 48 h after the cessation of saline or chronic cocaine treatment in rats, using the defensive burying paradigm and the elevated plus-maze. METHODS: Rats received daily injections of cocaine (20 mg/kg IP, for 14 consecutive days) or vehicle. Forty-eight hours after the last injection, animals were tested in the plus-maze and then in the defensive burying paradigm. In a second experiment, intracerebroventricular (ICV) cannulae were implanted at the lateral ventricle. Animals were allowed a 1-week period for recovery before starting the chronic drug treatment. The defensive burying testing took place 48 h after cessation of the treatment. The CRF antagonist [DPhe12, Nle21,38, CalphaMe Leu37] r/h CRF(12-41), (also known as D-phe CRF(12-41)) (0.04, 0.2 and 1.0 microg/5 microl) was injected 5 min before the 15-min testing. RESULTS: An "anxiogenic-like" effect following chronic cocaine treatment was demonstrated with the defensive burying paradigm, but not with the elevated plus-maze. This "anxiety-like" response was attenuated by ICV pretreatment with the CRF antagonist D-Phe CRF(12-41), with the highest dose of the CRF antagonist reversing the observed "anxiogenic-like" response. CONCLUSIONS: These data suggest that brain CRF may be substantially involved in the development of "anxiety-like" responses related to cocaine withdrawal and could be important for future drug dependence treatments.

Animals↗
PubMed1999

Differential effects of withdrawal from chronic amphetamine or fluoxetine administration on brain stimulation reward in the rat--interactions between the two drugs.

RATIONALE: Withdrawal from chronic amphetamine administration is characterized by deficits in reward that resemble some symptoms of depression. Nevertheless, the effects of long-term administration and withdrawal from other drugs, such as fluoxetine, that have the potential to elevate mood in depressed individuals have not been characterized. OBJECTIVES: The purpose of this study was to characterize the effects of withdrawal from chronic amphetamine or fluoxetine administration on central reward function. Furthermore, the effects of acute or chronic pretreatment with fluoxetine on responsiveness to an acute amphetamine challenge were examined to identify potential interactions between the two drugs. METHODS: A rate-independent discrete-trial threshold procedure was used to characterize self-stimulation behavior in rats prepared with bipolar electrodes in the medial forebrain bundle. RESULTS: Elevations in intracranial self-stimulation (ICSS) thresholds, reflecting a decrease in the reward value of the stimulation, were associated with withdrawal from various chronic amphetamine treatment regimens (1-5 mg/kg, three injections per day for 1, 2, 4 or 6 days). The magnitude and duration of threshold elevations were proportional to the duration and dose of amphetamine treatment prior to withdrawal. In contrast, no alterations in ICSS thresholds were associated with withdrawal from chronic fluoxetine treatment (5 mg/kg/day for 15 days). While neither acute nor chronic administration of fluoxetine alone altered ICSS thresholds, chronic pretreatment with fluoxetine blocked the threshold-lowering effect of acute amphetamine administration (4 mg/kg), but acute pretreatment did not. Amphetamine-induced decreases in response latency, a measure of motor performance, were not affected by either chronic or acute fluoxetine pretreatment. CONCLUSIONS: The results of these experiments suggest that chronic fluoxetine treatment may induce adaptive changes in serotonergic transmission that, in themselves, do not alter the function of central reward processes, but may alter the ability of amphetamine to potentiate ICSS reward. In addition, the lack of change in ICSS thresholds during withdrawal from the chronic fluoxetine treatment regimen used suggests that withdrawal from all mood-altering drugs may not necessarily produce changes in central reward functions.

Amphetamine↗
PubMed1999

Long-lasting increase in the set point for cocaine self-administration after escalation in rats.

RATIONALE: When access time to a continuous schedule of drug self-administration is restricted, animals tend to limit intake to a certain level over time and across doses. This observation suggests an endogenous constraint or set point that determines the individual's preferred level of pharmacological effects. OBJECTIVES: To assess whether the transition to increased levels of drug intake is associated with a change in set point. METHODS: Two groups of rats were trained on a 1-h continuous schedule of cocaine self-administration (250 microg/injection), after which access to cocaine was increased to 6 h in one group (Long Access or LgA rats) or kept to 1 h in the other group (Short Access or ShA rats). After 22 sessions on this regimen, different doses of cocaine were tested (31.25, 62.5, 125, and 250 microg/injection). For each dose, the post-response time-out period was reduced to 4 s to reduce any temporal limitations on self-injections and subjects were tested several times. RESULTS: In LgA rats, the first hour intake escalated over time and eventually reached a level 200% greater than that of ShA rats. Though all rats maintained relatively constant intake across doses, LgA rats took nearly two times as much cocaine than ShA rats. When access to cocaine for LgA rats was reduced to 1 h, intake returned very slowly toward pre-escalation levels but was still elevated even after 2 months of reduced availability. CONCLUSIONS: These data suggest that the transition to escalated levels of intake is associated with a long-lasting change in cocaine set point.

Animals↗
PubMed1999

A dopamine D1 agonist elevates self-stimulation thresholds: comparison to other dopamine-selective drugs.

The effects of the high-efficacy D1 receptor agonist SKF 81297 and the D2/3 receptor agonist 7-OH-DPAT on brain stimulation reward thresholds and on response latencies in responding for the stimulation, were compared to the effects of subtype-selective receptor antagonists and a dopamine uptake blocker. SKF 81297 produced dose-dependent elevations in reward thresholds but did not alter response latencies. In contrast, 7-OH-DPAT produced inconsistent reward threshold elevations, yet dose dependently increased response latencies. Both the dopamine D1 receptor antagonist SCH 23390 and the D2 antagonist raclopride elevated reward thresholds, but only raclopride significantly increased response latencies. The dopamine uptake inhibitor GBR 12909 lowered reward thresholds and did not influence response latencies. The present results provide a clear demonstration that a selective, high-efficacy D1 receptor agonist elevates brain stimulation reward thresholds without producing performance deficits. Furthermore, it was observed that the effects upon reward measures of D1-selective compounds, but not D2/D3-selective compounds, are dissociable from their effects upon response latency in this task. These results are discussed with regard to a distinction between the effects of indirect and direct dopamine agonists on reward thresholds, a distinction that does not depend upon the subtype-selectivity of the direct agonists tested.

Animals↗
PubMed1999

Blockade of nicotine self-administration with nicotinic antagonists in rats.

The reinforcing properties of a variety of drugs abused by humans have been investigated using the technique of intravenous self-administration in the rat. To examine the effect of nicotine dose on nicotine self-administration, Wistar rats were allowed to self-administer various doses of nicotine using a within-subjects Latin square design. An inverted U-shaped dose response curve was obtained, with the highest rates of responding at the 0.03 mg/kg/inf dose. With 1-h daily nicotine self-administration sessions, rats did not appear dependent on nicotine 24 h later, as indicated by the absence of somatic signs of withdrawal after subcutaneous injection of a nicotinic acetylcholine receptor antagonist, mecamylamine (0.57 mg/kg). In another set of studies, pretreatment with subcutaneous mecamylamine or dihydro-beta-erythroidine, two nicotinic acetylcholine receptor antagonists, resulted in significant dose-dependent reductions in nicotine self-administration, at two nicotine doses (0.03 and 0.06 mg/kg/inf). These results indicate that nicotine is an effective reinforcer in Wistar rats under the present parameters, and that these reinforcing effects are mediated by activation of nicotinic acetylcholine receptors.

Animals↗
PubMed1999

The amygdala mediates the anxiolytic-like effect of the neurosteroid allopregnanolone in rat.

The neurosteroid allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one) possesses clear anxiolytic-like effects. Other neurosteroids namely pregnenolone sulfate (PREG-S) and dehydroepiandrosterone sulfate (DHEA-S) influence anxiety-related behavior differently. In the present study, the implication of the amygdala, a key structure in mechanisms of fear and anxiety, was investigated as a potential neural substrate for the effects of neurosteroids on anxiety-like behavior in rat. Animals implanted with bilateral cannulae aimed at the central nucleus of the amygdala (CeA) and infused with neurosteroids, were tested in two animal models of anxiety. Allopregnanolone (8 microg/side) produced a significant increase in responding suppressed by punishment in the conflict test. In the elevated plus maze, allopregnanolone (8 microg/side) induced a significant increase in the time spent and the number of entries in open arms compared with the vehicle-infused controls. No significant changes in punished and unpunished responding of the conflict test were observed with PREG-S (0.001-8 microg/side) and DHEA-S (2-8 microg/side) administered into the CeA or into the lateral ventricle (1-20 microg). The results reveal the lack of activity of PREG-S and DHEA-S in the operant conflict test, but suggest that the central nucleus of the amygdala is a key region involved in the mechanisms underlying the anxiolytic-like action of allopregnanolone.

Amygdala↗
PubMed1999

Differential expression of response-disruptive and somatic indices of opiate withdrawal during the initiation and development of opiate dependence.

The current study examined the conditions that are necessary and sufficient for the initiation and progression of acute morphine dependence using two indices of opiate withdrawal: suppression of operant response rates and a somatic withdrawal rating scale. Separate groups of rats were pretreated with morphine (5 mg/kg, s.c.) a total of three times at intervals of 24 h, 1, 3, or 6 weeks. Rats received a single dose of naloxone 4 h after each morphine pretreatment. Naloxone-induced suppression of operant responding (0.33 mg/kg, s.c.) was significantly potentiated with repeated exposure to morphine even at the 6-week inter-treatment interval (ITI). At 24-h, 1-week and 3-week ITIs, rats treated with naloxone only after the third and final morphine pretreatment showed similar suppression of operant responding following naloxone to rats treated with naloxone after all three morphine pretreatments. However, at the 6-week ITI, the response-disruptive effects of naloxone administered for the first time after the third morphine pretreatment were no greater than the effects of naloxone administered after a single morphine pretreatment. In contrast to results seen with suppression of operant responding as the withdrawal index, potentiation of somatic signs of withdrawal was observed only at the 24-h ITI. These results indicate that a neuroadaptive state resembling opiate dependence can be initiated after just one injection of morphine, and that the response-disruptive effects of naloxone appear to be a particularly sensitive index of the initiation and progression of acute opiate dependence.

Animals↗
PubMed1999

Stress, corticotropin-releasing factor, and drug addiction.

The neuropeptide corticotropin-releasing factor (CRE) and related neuropeptides not only mediate hormonal responses to stressors but also have a neurotropic role in the central nervous system to mediate behavioral responses to stressors. CRF antagonists effectively block CRF responses and have effects opposite those of CRF in many stress-related situations. Recent advances suggest that in addition to CRF itself there is another CRF-related neuropeptide, urocortin, that may be involved in stress-related responses, particularly those involving appetite. At least two CRF receptors have been discovered to date, CRF-1 and CRF-2. CRF may be involved in various aspects of the addiction cycle associated with drugs of abuse. CRF appears to be activated during stress-induced reinstatement of drug taking as well as acute withdrawal from all major drugs of abuse. CRF is hypothesized to be part of an allostatic change leading to vulnerability to relapse during prolonged abstinence from drugs of abuse.

Animals↗
PubMed1999

Total neurochemical lesion of noradrenergic neurons of the locus ceruleus does not alter either naloxone-precipitated or spontaneous opiate withdrawal nor does it influence ability of clonidine to reverse opiate withdrawal.

It has been suggested that an increase firing rate of noradrenergic neurons of the locus ceruleus is responsible for the opiate withdrawal syndrome. However, lesion studies have indicated that the noradrenergic neurons of the locus ceruleus are not essential for either the expression or suppression by clonidine of opiate withdrawal. The present study was designed to determine the effect of the almost complete 6-hydroxydopamine lesion of noradrenergic neurons (94%) of the locus ceruleus on various components of the opiate withdrawal syndrome and on its protection by clonidine. Morphine dependence was induced by s.c. implantation of morphine pellets (2 x 75 mg base). The following paradigms were used: 1) naloxone-induced conditioned place aversion, 2) naloxone-precipitated acute opiate withdrawal syndrome, 3) nycthemeral locomotor activity as a measure of spontaneous opiate withdrawal. The results showed that quasi-total lesion of noradrenergic neurons of the locus ceruleus did not modify opiate dependence as revealed by naloxone-induced conditioned place aversion and the expression of an acute morphine withdrawal syndrome. Moreover, clonidine prevented the opiate withdrawal syndrome in both lesioned and sham-operated rats, suggesting that the action of clonidine is certainly mediated through postsynaptic alpha(2)-adrenoceptor stimulation. Finally, the nycthemeral locomotor activity during spontaneous morphine withdrawal did not differ between the lesioned and the sham-operated rats.

Adrenergic alpha-Agonists↗
PubMed1999

Operant self-administration of sweetened versus unsweetened ethanol: effects on blood alcohol levels.

BACKGROUND: Sweeteners are often added to ethanol solutions to increase ethanol intake. However, literature on studies that use human subjects and laboratory animals suggests that sucrose, other sugars, and carbohydrate-rich foods alter ethanol absorption and metabolism, which leads to lower blood alcohol levels (BAL) relative to ethanol absorbed alone. This experiment was designed to test whether the addition of the nutritive sweetener sucrose, or the nonnutritive sweetener saccharin, to a 10% ethanol solution, self-administered in an oral operant paradigm, affected BAL in rats relative to self-administration of an unsweetened 10% ethanol solution. METHODS: All rats were trained to lever press for ethanol by use of a saccharin fading procedure. Half of the rats then received 30-min sessions in which ethanol + 2% sucrose and water were available and were alternated daily with sessions in which ethanol + 0.2% saccharin and water were available. The other half of the rats went on to receive daily sessions of unsweetened ethanol and water. BAL were taken after these standard daily sessions as well as after a 1-week period of alcohol deprivation (to enhance ethanol intake). RESULTS: Rats responded for more ethanol + sucrose than unsweetened ethanol, but had lower BAL per gram ethanol consumed in both the baseline test and alcohol deprivation effect test. No effect of saccharin on BAL was detected. An additional experiment that examined the effects of four concentrations of both sucrose and saccharin on self-administration of ethanol and BAL showed that, whereas rats consumed more ethanol + sucrose than ethanol + saccharin, BAL were significantly lower per gram ethanol consumed in the sucrose group. CONCLUSIONS: These results confirm previous reports and suggest that the addition of sucrose to an ethanol solution can result in lower BAL relative to unsweetened ethanol in an oral operant self-administration paradigm.

Alcohol Drinking↗
PubMed1999

Central administration of an opiate antagonist decreases oral ethanol self-administration in rats.

BACKGROUND: Opioid peptides have been implicated in various behavioral actions of alcohol, including its reinforcing effects; however, the role of specific brain sites for these actions remains to be explored. The present study examined the effects of intracerebroventricular (ICV) or intracerebral injections of an opiate antagonist (methylnaloxonium) on ethanol self-administration. The nucleus accumbens and amygdala were selected as intracerebral sites because these regions have been implicated in the reinforcing effects of drugs of abuse. METHODS: Male Wistar rats were trained in a limited-access paradigm (30 min/day) to respond for ethanol (10% w/v) or water in a two-lever free-choice condition using a saccharin fading procedure. After the establishment of stable baseline responding for ethanol, animals were implanted stereotaxically with a guide cannula above the lateral ventricle or with bilateral guide cannulae either above the nucleus accumbens or amygdala. After postoperative recovery of stable baseline responding, the rats were tested 15 min after ICV or intracerebral microinjections of methylnaloxonium (0-2000 ng). RESULTS: Injections of methylnaloxonium into the amygdala significantly reduced responding for ethanol at doses of 250-500 ng. Injections of methylnaloxonium into the nucleus accumbens significantly reduced responding for ethanol at doses of 500-1000 ng, whereas higher doses were needed ICV. CONCLUSIONS: These results provide evidence that opioid receptors located in the amygdala and nucleus accumbens may be involved in the regulation of ethanol self-administration.

Amygdala↗
PubMed1999

Animal models of craving: a roundtable discussion.

Five experts respected for their work in the development of animal models of alcohol craving offer their perspectives in a roundtable discussion format. The panel members discuss the various definitions and theories of alcohol craving and the benefits and limitations of using animal models to study alcohol craving in humans. Animal models have helped further the understanding of craving by providing information about behavior associated with craving. Animal models do have limitations, however. The fact that animals cannot "talk" about their feelings poses difficulties for researchers seeking to map an animal analog of craving onto the human experience.

Alcoholism↗
PubMed1999

Cannabinoid receptor antagonist SR141716A decreases operant ethanol self administration in rats exposed to ethanol-vapor chambers.

AIM: To study the potential role of dependence status on CB1-mediated blockade of ethanol self-administration. METHODS: We examined the effects of the cannabinoid antagonist SR141716A (0, 0.03, 0.3, and 3 mg/kg) on operant ethanol (10% v/v) self-administration in male Wistar rats that were made ethanol-dependent by chronic (14 d) exposure to ethanol vapor-chambers or exposed to air in identical vapor chambers. RESULTS: Dependent animals responded more for ethanol than did air control nondependent rats. The acute administration of a 3 mg/kg dose of SR141716A almost suppressed ethanol self-administration only in ethanol dependent animals. However, operant responses for food were not affected by the administration of SR141716A. CONCLUSION: These results further support that cannabinoid CB1 receptor blockade may have a potential utility for the treatment of alcoholism.

Alcoholism↗