Repeated cocaine modifies the neuroendocrine responses to the 5-HT1C/5-HT2 receptor agonist DOI.
Endocrine responses to the serotonin (5-HT) 5-HT1C/5-HT2 agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) were utilised to evaluate cocaine-induced alterations in postsynaptic 5-HT receptor function. Rats received cocaine HCl (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 dependently increased the plasma concentrations of each hormone. Cocaine potentiated the DOI-induced elevations of plasma ACTH, corticosterone 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 supersensitive following repeated cocaine. In contrast, the 5-HT2 receptor-mediated response for oxytocin secretion is subsensitive. The cocaine-induced changes in postsynaptic 5-HT receptor function are likely a consequence of deficits in the function of 5-HT nerve terminals, that we have documented previously.
Levy
A D
AD
Department of Pharmacology, Stritch School of Medicine, Loyola University of Chicago, Maywood, IL 60153.
Li
Q
Q
Alvarez Sanz
M C
MC
Rittenhouse
P A
PA
Brownfield
M S
MS
Van de Kar
L D
LD
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D006728:Hormones / Q000097:blood*; D008297:Male; D010121:Oxytocin / Q000097:blood; D011388:Prolactin / Q000097:blood; D011719:Pyrazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D012083:Renin / Q000097:blood; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000662:Amphetamines; D006728:Hormones; D011719:Pyrazines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D010121:Oxytocin; C014896:6-chloro-2-(1-piperazinyl)pyrazine; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D012083:Renin; D003042:Cocaine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D003345:Corticosterone