Serotonergic function in cocaine addicts: prolactin responses to sequential D,L-fenfluramine challenges

Preclinical studies have shown that cocaine produces alterations in serotonergic function but our knowledge of the serotonergic alterations due to cocaine abuse in humans is still fragmentary. We therefore assessed the central serotonergic responsivity of cocaine addicts and control subjects by neuroendocrine challenges with the serotonin releaser and reuptake inhibitor D,L-fenfluramine (FEN).

Plasma prolactin levels following a 60 mg oral dose of FEN and placebo were studied in 25 hospitalized male cocaine addicts and 13 healthy male subjects. Control subjects underwent one set of FEN/placebo challenges and cocaine addicts two sets of challenges, during the first and third weeks following cocaine discontinuation. Patients were divided into two subgroups as a function of presence (FH+) and absence (FH-) of a paternal history of substance abuse. The following comparisons were made: 1) Control subjects versus entire patient group and versus patient subgroups; 2) entire patient group and patient subgroups responses to first versus second challenges; 3) FH+ versus FH- patients' early responses and FH+ versus FH- patients' late responses.

The prolactin responses to FEN increased significantly in the entire patient group as time following cocaine discontinuation increased. The FH+ patients had significantly blunted early responses by comparison with FH- patients and control subjects. There was a more pronounced rebound of the responses of FH+ patients by comparison with those of FH- patients. As a result, comparisons of the late responses of FH+ and FH- patients and of FH+ patients and control subjects became nonsignificant.

Cocaine use appears to have an effect on the serotonergic mechanisms mediating prolactin release in humans. In the present study, this effect was more pronounced in a subgroup of patients with a paternal history of alcoholism or drug abuse. The greater blunting of the prolactin response observed within days of cocaine discontinuation followed by a greater rebound of this response 2 weeks later could indicate an increased vulnerability to the disruptive effects of cocaine in these patients.