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The present study assessed the efficacy of the cannabinoid CB1 receptor antagonist, SR-141716, in reducing voluntary ethanol intake in selectively bred Sardinian alcohol-preferring (sP) rats. Ethanol (10%, v/v) and food were available in daily 4 h scheduled access periods; water was present 24 h/day. The acute administration of a 2.5 and a 5 mg/kg dose of SR-141716 selectively reduced ethanol intake, whereas a 10 mg/kg dose of SR-141716 reduced to a similar extent both ethanol and food intake. These results suggest that the cannabinoid CB1 receptor is involved in the mediation of the ethanol-reinforcing effects in sP rats.

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These results are in close agreement with those of a preliminary clinical study and suggest that baclofen may constitute a novel therapeutic agent for alcoholism.

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BackgroundAlcohol dependence is a major public health problem characterized by recidivism, and medical and psychosocial complications. The cooccurrence of major depression in people entering treatment for alcohol dependence is common, and represents a risk factor for morbidity and mortality, which negatively influences treatment outcomes. ObjectivesTo assess the benefits and risks of antidepressants for the treatment of people with co-occurring depression and alcohol dependence. Search methodsWe searched the Cochrane Drugs and Alcohol Group Specialised Register (via CRSLive), Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from inception to July 2017. We also searched for ongoing and unpublished studies via ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (apps.who.int/ trialsearch/).All searches included non-English language literature. We handsearched references of topic-related systematic reviews and the included studies. Selection criteriaRandomized controlled trials and controlled clinical trials comparing antidepressants alone or in association with other drugs or psychosocial interventions (or both) versus placebo, no treatment, and other pharmacological or psychosocial interventions. Data collection and analysisWe used standard methodological procedures as expected by Cochrane. Main resultsWe included 33 studies in the review (2242 participants). Antidepressants were compared to placebo (22 studies), psychotherapy (two studies), other medications (four studies), or other antidepressants (five studies). The mean duration of the trials was 9.9 weeks (range 3 to 26 weeks). Eighteen studies took place in the USA, 12 in Europe, two in Turkey, and one in Australia. The antidepressant included in most of the trials was sertraline; other medications were amitriptyline, citalopram, desipramine, doxepin, escitalopram, fluoxetine, fluvoxamine, imipramine, mianserin, mirtazepine, nefazodone, paroxetine, tianeptine, venlafaxine, and viloxazine. Eighteen studies were conducted in Antidepressants for the treatment of people with co-occurring depression and alcohol dependence (Review)

The present paper describes the results of recent preclinical and clinical studies conducted in this laboratory in order to characterize the anti-alcohol properties of the GABA(B) receptor agonist, baclofen. At a preclinical level, the repeated administration of non-sedative doses of baclofen dose-dependently suppressed the acquisition and maintenance of alcohol drinking behavior in selectively bred Sardinian alcohol-preferring (sP) rats tested under the homecage, 2-bottle "alcohol vs water" choice regimen. Acute injection of baclofen completely blocked the temporary increase in voluntary alcohol intake occurring after a period of alcohol abstinence (the so-called alcohol deprivation effect, which models alcohol relapses in human alcoholics). Acute treatment with baclofen also dose-dependently suppressed extinction responding for alcohol (an index of motivation to consume alcohol) in sP rats trained to lever-press for oral alcohol self-administration. Taken together, these results suggest the involvement of the GABA(B) receptor in the neural substrate mediating alcohol intake and alcohol motivational properties in an animal model of excessive alcohol consumption. Further, acutely administered baclofen dose-dependently reduced the severity of alcohol withdrawal signs in Wistar rats made physically dependent upon alcohol. Preliminary clinical surveys suggest that the anti-alcohol properties of baclofen observed in rats may generalize to human alcoholics. Indeed, a double-blind survey demonstrated that repeated daily treatment with baclofen was associated, when compared to placebo, with a higher percentage of subjects totally abstinent from alcohol and a higher number of days of total abstinence. Treatment with baclofen also suppressed the number of daily drinks and decreased the obsessive and compulsive components of alcohol craving. Finally, a single non-sedative dose of baclofen resulted in the rapid disappearance of alcohol withdrawal symptomatology, including delirium tremens, in alcohol-dependent patients. In both clinical studies, baclofen was well tolerated with minimal side effects. These results suggest that baclofen may represent a potentially effective medication in the treatment of alcohol-dependent patients.