Cigarette Smoking Decreases the Prolactin Response to Serotonergic Stimulation in Subgroups of Alcoholics and Controls

Background: The prolactin response to serotonergic stimulation has been used as an index of central nervous system serotonin function. We evaluated the prolactin response to d,l‐fenfluramine to determine whether subtypes of alcoholics differed in prolactin responsivity compared with nonalcoholics and whether cigarette smoking affected prolactin response. Methods: One hundred ten healthy, abstinent men across four groups (controls [23% smokers]; alcoholics [72% smokers]; alcoholics with antisocial personality disorder [94% smokers]; nonalcoholic antisocials [88% smokers]) received d,l‐fenfluramine (100 mg orally) in a randomized, double‐blind, placebo‐controlled study. Plasma prolactin levels were obtained at baseline and at half‐hour intervals for 5 hr after fenfluramine/placebo administration. Plasma fenfluramine and norfenfluramine levels were obtained hourly. Results: Smokers had a blunted prolactin response to fenfluramine compared with nonsmokers without any alcoholism or antisocial personality effects. Using a cutoff point of Δ peak prolactin \u3c 10 ng/ml, more smokers (41/76, 54%) had a dampened response to fenfluramine than did nonsmokers (7/34, 21%) [X2(1)=10.6, p \u3c 0.003]. The percentage of low responders was greatest among smokers regardless of whether they were healthy controls, alcoholics, or antisocial. Multiple regression revealed that three variables—(1) number of pack‐years of smoking, (2) actual dosage of fenfluramine received, and (3) plasma norfenfluramine level obtained—explained 43% of the variance (R2= 0.43) in Δ prolactin area under the curve. Variables that included alcoholism diagnostic status, antisocial personality diagnostic status, and impulsive aggressive personality, depressive, and suicidal traits failed to explain any additional unique variance. Conclusions: Cigarette smoking blunted the prolactin response to a pharmacological challenge with d,l‐fenfluramine. Pharmacodynamic and pharmacokinetic factors related to smoking both appear to influence fenfluramine‐induced prolactin secretion. Phenotypes of alcoholics did not differ in their prolactin response to this serotonergic probe