Repeated cocaine modifies the neuroendocrine responses to the 5-HT_1C/5-HT₂ receptor agonist DOI

Endocrine responses to the serotonin (5-HT) 5-HT_ic(-/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.