Low-dose diazepam primes motivation for alcohol and alcohol-related semantic networks in problem drinkers.
Considerable research with animals indicates that the GABA-benzodiazepine (BZ) system plays a key role in alcohol reinforcement. However, only limited research appears to have assessed this issue directly in humans. The present study investigated whether low-dose diazepam would cross-prime motivation for alcohol in problem drinkers. Twelve male problem drinkers (Alcohol Dependence Scale; ADS score > or =9) received oral diazepam (5 mg) and placebo, in a counterbalanced manner on separate sessions. There were three measures of primed motivation for alcohol: self-reported desire for alcohol, consumption of placebo beer in an ostensible taste test procedure, and automatically executed vocal reading responses to Alcohol versus Neutral words on a computer-based task. Diazepam significantly increased beer consumption, and produced a marginally significant increase in reported desire for alcohol. On the reading task, diazepam significantly decreased response latency to Alcohol words relative to Neutral words. Latency to Alcohol words correlated significantly with beer consumption under the drug. Moreover, response latency to Alcohol words under the drug also predicted ADS scores. Thus, severity of dependence was directly linked with vulnerability to a BZ priming effect on motivation for alcohol. These findings provide direct evidence that the GABA-BZ system plays an important role in alcohol reinforcement in problem drinkers.
Clinical Neuroscience Section, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
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D000284:Administration, Oral; D000328:Adult; D000428:Alcohol Drinking; D000437:Alcoholism / Q000503:physiopathology*; D003975:Diazepam / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D018757:GABA Modulators / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009042:Motivation; D018079:Receptors, GABA / Q000502:physiology; D012054:Reinforcement, Psychology; D012660:Semantics
D018757:GABA Modulators; D018079:Receptors, GABA; D003975:Diazepam