Repeated cocaine modifies the neuroendocrine responses to the 5-HT1C/5-HT2 receptor agonist DOI

Andrew D. Levy, Qian Li, Maria C. Alvarez Sanz, Peter A. Rittenhouse, Mark S. Brownfield, Louis D. Van de Kar

Research output: Contribution to journalArticlepeer-review

Abstract

Endocrine responses to the serotonin (5-HT) 5-HTic(-/5-HT2 agonist (±)-l-(2,5-dimcthoxy-4-iodophenyl)-2-aminopropane (DOI) were utilised to evaluate cocaine-induced alterations in postsynaptic 5-HT receptor function. Rats received cocaine HC1 (0, 5 or 15 mg/kg i.p.) twice daily for 7 days. Effects of DOI (0, 0.5, 2 or 10 mg/kg i.p.) on plasma adrenocorticotropic hormone (ACTH), corticosterone, prolactin, oxytocin and renin concentrations were assessed 42 h after the final cocaine injection. DOI dose dcpcndcntly increased the plasma concentrations of each hormone. Cocaine potentiated the DOI-induced elevations of plasma ACTH, corticostcrone and prolactin concentrations. In contrast, the oxytocin response was reduced, and the renin response was unaltered by cocaine exposure. The data suggest that 5-HT2 receptor-mediated responses for ACTH, corticosterone and prolactin secretion become superscnsitivc following repeated cocaine. In contrast, the 5-HT2, receptor-mediated response for oxytocin secretion is subscnsitive. The cocaine-induced changes in posisynaptic 5-HT receptor function are likely a consequence of deficits in the function of 5-HT nerve terminals, that we have documented previously.

Original languageEnglish (US)
Pages (from-to)121-127
Number of pages7
JournalEuropean Journal of Pharmacology
Volume221
Issue number1
DOIs
StatePublished - Oct 6 1992
Externally publishedYes

Keywords

  • 5-HT (5-hydroxytryptaminc, serolonin)
  • ACTH (adrcnocorticotropic hormone)
  • Cocaine
  • Oxytocin
  • Prolactin
  • Renin

ASJC Scopus subject areas

  • Pharmacology

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