Serum prolactin response to the serotonin agonist D-fenfluramine were measured in 19 DSM-111-R male alcoholics, 2.5 or more weeks postalcohol withdrawal. Prolactin responses were compared with nine healthy nonalcoholic male controls. After an overnight fast, each subject received 30 mg of D-fenfluramine orally, and serial samples of serum prolactin were taken over a 4-hr period. D-fenfluramine caused a significantly attenuated peak delta-prolactin response in the alcoholics relative to the controls (p = 0.05). A repeated-measures ANOVA of delta-prolactin yielded a significant within-subjects effect of time (p < 0.05), a within-subjects effect of group that reached significance (p = 0.05), and a nonsignificant group by time interaction. The delta-prolactin value at time points 60 and 240 min postadministration of the probe was significantly attenuated in the alcoholic group, with p < 0.05. There was also some evidence for a diminished serotonergic response in those alcoholics with a negative family history. The delta-prolactin response did not correlate with subjects' age, duration of alcohol use, duration of abstinence from alcohol, severity of alcohol dependence, or age of onset. Results imply a relative subsensitivity of the serotonin system in postwithdrawal alcoholics, and this may be primarily of the 5-HT2 receptor.

Dopamine D2 receptor sensitivity was assessed in the postwithdrawal period in alcoholics. Growth hormone (GH) responses to dopamine D2 agonist bromocriptine were measured in eight DSM-III-R alcohol-dependent subjects who were 2 weeks or more postalcohol withdrawal. Their responses were compared with eight nonalcoholic controls. After an overnight fast, each subject received 1.25 mg of bromocriptine orally, and serial samples of GH were taken over a 3-hr period. There was a significantly blunted delta GH response (mean +/- SE) in the alcoholic group, 2.3 mU/liter (+/- 1.4) relative to controls, 7.7 mU/liter (+/- 1.2) (t = 2.96, df = 14, p = 0.01). There was a significantly blunted peak GH response (mean +/- SE) in the alcoholic group, 5.36 mU/liter (+/- 2.1) relative to controls, 9.04 mU/liter (+/- 5.0). This difference also reached statistical significance (t = 2.32, df = 14, p = 0.035). A repeated-measures ANOVA yielded a significant within-subjects effect of time [F(4,54) = 4.08, p = 0.0057], a significant within-subjects effect of group [F(1,14) = 5.6, p = 0.0329], and an almost significant group x time interaction [F(4,54) = 2.45, p = 0.056]. This result implies a relative dopamine D2 receptor subsensitivity in alcoholics in the postwithdrawal period.