Modulation of alcohol craving induced by challenge stimuli may predict the efficacy of new
pharmacotherapies for
alcoholism. We evaluated two pharmacological challenges, the α(2)-adrenergic antagonist
yohimbine, which reinstates alcohol seeking in rats, and the serotonergic compound
meta-chlorophenylpiperazine (mCPP), previously reported to increase alcohol craving in alcoholics. To assess the predictive validity of this approach, the approved
alcoholism medication
acamprosate was evaluated for its ability to modulate challenge-induced cravings. A total of 35 treatment seeking alcohol dependent inpatients in early abstinence were randomized to placebo or
acamprosate (2997 mg daily). Following two weeks of medication, subjects underwent three challenge sessions with
yohimbine, mCPP or saline infusion under double blind conditions, carried out in counterbalanced order, and separated by at least 5 days. Ratings of cravings and anxiety, as well as biochemical measures were obtained. In all, 25 subjects completed all three sessions and were included in the analysis. Cravings were modestly, but significantly higher following both
yohimbine and mCPP challenge compared with saline infusion. The mCPP, but not
yohimbine significantly increased anxiety ratings. Both challenges produced robust
ACTH,
cortisol and
prolactin responses. There was a significant correlation between craving and the degree of
alcoholism severity.
Acamprosate administration did not influence craving. Both
yohimbine and mCPP challenges lead to elevated alcohol craving in a clinical population of alcoholics, and these cravings correlate with
alcoholism severity. Under the experimental conditions used, alcohol cravings induced by these two stimuli are not sensitive to
acamprosate at clinically used doses.