A human laboratory pilot study with baclofen in alcoholic individuals

作者：Leggio Lorenzo^*; Zywiak William H; McGeary John E; Edwards Steven; Fricchione Samuel R; Shoaff Jessica R; Addolorato Giovanni; Swift Robert M; Kenna George A

来源：Pharmacology Biochemistry and Behavior, 2013, 103(4): 784-791.

DOI：10.1016/j.pbb.2012.11.013

• Baclofen
• Alcoholism
• Cue-reactivity
• Alcohol self-administration
• Biobehavioral mechanisms
• Genetic polymorphisms

Preclinical and clinical studies show that the GABA(B) receptor agonist baclofen may represent a pharmacotherapy for alcohol dependence (AD). However, the mechanisms by which baclofen affects drinking are not well characterized; thus this pilot study investigated possible baclofen%26apos;s biobehavioral mechanisms. The design was a double-blind controlled randomized human laboratory pilot study. Fourteen non-treatment seeking alcohol-dependent heavy drinking subjects received either baclofen 10 mg t.i.d. or an active placebo (cyproheptadine 2 mg t.i.d., to control for sedation) for a 7-day period. At day 8, participants performed an alcohol cue-reactivity (CR) followed by an alcohol self-administration (ASA). Additionally, we explored possible moderators that might guide future larger studies, i.e. anxiety, family history and onset of alcoholism, and D4 dopamine receptor (DRD4) and 5-HTTLPR polymorphisms. The main results were a significant effect of baclofen for increasing stimulation (p=.001) and sedation (p%26lt;.01). Furthermore, when drinking during the ASA and the 2 days before was analyzed as a composite variable, there was a significant effect of baclofen to reduce alcohol consumption (p%26lt;.01). As for the exploratory analyses, baclofen%26apos;s effects to increase alcohol sedation and to reduce alcohol consumption were limited to those individuals with DRD %26gt;= 7 repeats (DRD4L). Yet, baclofen%26apos;s effects on alcohol consumption were also moderated by 5-HTTLPR LL genotype. In conclusion, baclofen%26apos;s ability to reduce alcohol drinking may be related to its effects on the biphasic effects of alcohol, but larger studies are needed to confirm these preliminary findings. Published by Elsevier Inc.

• 出版日期2013-2