Serotonergic responsiveness in human cocaine users.
BACKGROUND
Animal experiments show that repeated cocaine injections induce changes in brain serotonin (5-hydroxytryptamine, or 5-HT) function which can be detected by altered neuroendocrine responsiveness to serotonergic drug challenge. Studies of human cocaine users given a serotonergic challenge have produced inconsistent results.


METHODS
Hormone responses evoked by the 5-HT releaser D,L-fenfluramine (FEN) were examined in eight human cocaine users who resided on a closed research ward. FEN (60 mg oral) was given after a 7-day cocaine-free period and 3 days after a 5-day period of daily double-blind administration of intranasal cocaine (96 mg) and active placebo (4 mg cocaine). Plasma cortisol and prolactin levels were measured after FEN challenges, and after cocaine and placebo administration.


RESULTS
Cocaine significantly elevated plasma cortisol levels to a similar degree on the first and fifth days of administration, but did not alter prolactin levels on either day. The first FEN challenge significantly increased plasma prolactin and cortisol, whereas the second challenge increased only prolactin.


CONCLUSIONS
Intranasal cocaine increases plasma cortisol without affecting prolactin, with no evidence for tolerance. The reduction in FEN-induced cortisol secretion after cocaine exposure suggests that deficits in 5-HT transmission during early cocaine abstinence might contribute to the maintenance of drug dependence.
Ghitza
Udi E
UE
Clinical Pharmacology and Therapeutics Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
Rothman
Richard B
RB
Gorelick
David A
DA
Henningfield
Jack E
JE
Baumann
Michael H
MH
D000328:Adult; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D005260:Female; D005277:Fenfluramine / Q000008:administration & dosage*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D011388:Prolactin / Q000097:blood; D012701:Serotonin / Q000502:physiology*; D018490:Serotonin Agents / Q000008:administration & dosage*; D013997:Time Factors
D018765:Dopamine Uptake Inhibitors; D018490:Serotonin Agents; D005277:Fenfluramine; D012701:Serotonin; D011388:Prolactin; D003042:Cocaine; D006854:Hydrocortisone