Cocaine-induced elevation of plasma adrenocorticotropin hormone and corticosterone is mediated by serotonergic neurons

A. D. Levy, Q. Li, J. E. Kerr, P. A. Rittenhouse, G. Milonas, T. M. Cabrera, G. Battaglia, M. C. Alvarez Sanz, L. D. Van de Kar

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We investigated the hypothesis that cocaine-induced elevations of plasma adrenocorticotropin hormone (ACTH) and corticosterone are mediated by brain serotonin (5-HT) neurons. Adult male rats were pretreated with the 5-HT depleting agent p-chlorophenylalanine, the 5-HT neurotoxin 5,7- dihydroxytryptamine, the partial 5-HT(1A) agonist 8-{2-[4-(2-methoxyphenyl)- 1-piperazinyl]ethyl}-8-azaspirol[4,5]-decane-7,9-dione (BMY 7378) or the 5- HT(1C/2) antagonist ritanserin. The effects of cocaine (2-15 mg/kg, i.p.) on plasma ACTH and corticosterone were then examined. Cocaine dose-dependently increased ACTH and corticosterone concentration. This increase was prevented by 5-HT depletion with PCPA and by destruction of 5-HT neurons with i.c.v. injections of 5,7-dihydroxytryptamine. The cocaine-induced elevation of ACTH and corticosterone was not significantly modified by administration of the partial 5-HT(1A) agonist BMY 7378, suggesting that 5-HT(1A) receptors probably do not mediate ACTH and corticosterone secretion. However, pretreatment with the 5-HT2/5-HT(1C) antagonist ritanserin virtually eliminated the cocaine-induced elevation of corticosterone. To determine whether these effects of cocaine are centrally mediated, conscious rats received cocaine injections into the cerebral ventricle through chronically implanted cannulas. Plasma ACTH concentrations were dose-dependently increased, whereas low doses (50 μg/kg, i.c.v.) produced a maximal increase in corticosterone concentration. These data indicate that the cocaine-induced stimulation of ACTH and corticosterone secretion is mediated by 5-HT neurons in brain, and furthermore, that 5-HT2 or 5-HT(1C) receptors are responsible for this effect.

Original languageEnglish (US)
Pages (from-to)495-500
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number2
StatePublished - 1991
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


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