SPECIFICITY OF ETHANOLLIKE EFFECTS ELICITED BY SEROTONERGIC AND NORADRENERGIC MECHANISMS

Background: This study evaluated the specificity of the ethanollike ef fects of the serotonergic receptor partial agonistm-chlorophenylpipera zine hydrochloride (MCPP) relative to the alpha(2)-adrenergic receptor antagonist yohimbine hydrochloride and the placebo in recently detoxi fied alcoholics. It also examined the relationship between ethanollike discriminative properties and the induction of craving in these patie nts. Both MCPP and yohimbine are anxiogenic in humans; thus, this stud y evaluated the role of anxiogenic and ethanollike effects in the elic itation of craving. Methods: Twenty-two male inpatients who met DSM-II I-R criteria for alcohol dependence and who had not consumed alcohol f or 12 to 26 days prior to the study completed 3 days of testing that i nvolved the intravenous infusion of MCPP (0.1 mg/kg), yohimbine hydroc hloride (0.4 mg/kg), or a saline solution over 2 weeks under double-bl ind conditions. Ethanollike subjective effects were assessed using the Sensation Scale and visual analog scales to measure the degree of sim ilarity to the effects of ethanol, cocaine, and marijuana. Five compon ents of craving for alcohol were assessed using visual analog scales. The effects of the drugs on mood were assessed using visual analog sca les. Plasma levels of cortisol, prolactin, and 3-methoxy-4-hydroxyphen yl-ethyleneglycol were also measured during the test days. Results: m- Chlorophenylpiperazine and yohimbine produced significant increases co mpared with placebo in Sensation Scale scores and the visual analog sc ale score for nervousness. However, the effects of MCPP were rated as more similar to those of ethanol, cocaine, and marijuana than were tho se of either yohimbine or placebo. Also, MCPP but not yohimbine or pla cebo significantly increased craving for alcohol. Yohimbine and MCPP i ncreased plasma prolactin and cortisol levels relative to placebo, whe reas only yohimbine increased plasma 3-methoxy-4-hydroxyphenylethylene glycol levels. Conclusions: m-Chlorophenylpiperazine produced ethanoll ike effects and alcohol craving in recently detoxified alcoholics. Yoh imbine increased Sensation Scale scores but was not recognized as etha nollike by patients. Although both drugs produced comparable levels of nervousness, yohimbine did not increase craving for alcohol. These da ta further implicate serotonergic systems in the discriminative proper ties of ethanol. and may indicate a serotonergic contribution to cravi ng. Noradrenergic systems contributed to the discriminative properties of ethanol but not to those features of ethanol response that were sa lient to craving in this population.