title: Pharmacologically induced alcohol craving in treatment seeking alcoholics correlates with alcoholism severity, but is insensitive to acamprosate.
abstract: 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.
authors.affiliation: Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-1108, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Umhau
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Schwandt
authors.forename: Julie
authors.initials: J
authors.lastname: Usala
authors.forename: Christopher
authors.initials: C
authors.lastname: Geyer
authors.forename: Erick
authors.initials: E
authors.lastname: Singley
authors.forename: David T
authors.initials: DT
authors.lastname: George
authors.forename: Markus
authors.initials: M
authors.lastname: Heilig
mesh_terms: D000077443:Acamprosate; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000009:adverse effects; D000328:Adult; D000427:Alcohol Deterrents / Q000008:administration & dosage*; D020268:Alcohol-Induced Disorders, Nervous System / Q000188:drug therapy* / Q000523:psychology; D000437:Alcoholism / Q000188:drug therapy* / Q000523:psychology; D001007:Anxiety / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects*; D010919:Placebos; D017366:Serotonin Receptor Agonists; D012720:Severity of Illness Index; D013654:Taurine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D017211:Treatment Failure; D015016:Yohimbine / Q000009:adverse effects*
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D000427:Alcohol Deterrents; D010879:Piperazines; D010919:Placebos; D017366:Serotonin Receptor Agonists; D013654:Taurine; D015016:Yohimbine; D000077443:Acamprosate; C015068:1-(3-chlorophenyl)piperazine