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

<p> <strong> Background: </strong> The prolactin response to serotonergic stimulation has been used as an index of central nervous system serotonin function. We evaluated the prolactin response to <em> d,l </em> &hyphen;fenfluramine to determine whether subtypes of alcoholics differed in prolactin responsivity compared with nonalcoholics and whether cigarette smoking affected prolactin response.</p><p> <strong> Methods: </strong> 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 <em> d,l </em> &hyphen;fenfluramine (100 mg orally) in a randomized, double&hyphen;blind, placebo&hyphen;controlled study. Plasma prolactin levels were obtained at baseline and at half&hyphen;hour intervals for 5 hr after fenfluramine/placebo administration. Plasma fenfluramine and norfenfluramine levels were obtained hourly.</p><p> <strong> Results: </strong> Smokers had a blunted prolactin response to fenfluramine compared with nonsmokers without any alcoholism or antisocial personality effects. Using a cutoff point of &Delta; peak prolactin &lt; 10 ng/ml, more smokers (41/76, 54%) had a dampened response to fenfluramine than did nonsmokers (7/34, 21%) [ <em> X </em> ² (1)=10.6, <em> p </em> &lt; 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&mdash;(1) number of pack&hyphen;years of smoking, (2) actual dosage of fenfluramine received, and (3) plasma norfenfluramine level obtained&mdash;explained 43% of the variance ( <em> R </em> ² = 0.43) in &Delta; 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.</p><p> <strong> Conclusions: </strong> Cigarette smoking blunted the prolactin response to a pharmacological challenge with <em> d,l </em> &hyphen;fenfluramine. Pharmacodynamic and pharmacokinetic factors related to smoking both appear to influence fenfluramine&hyphen;induced prolactin secretion. Phenotypes of alcoholics did not differ in their prolactin response to this serotonergic probe.</p>