Embryonic cocaine exposure and corticosterone: Serotonin(2) receptor mediation

Cocaine activates the mature hypothalamic-pituitary-adrenal (HPA) axis, inc reasing corticosterone concentrations in animals and humans and serotonin(2 ) receptors (5-HT2) are involved in this effect. Although prenatal cocaine exposure is associated with altered responsiveness of the HPA axis to "stre ss" and serotonergic compounds postnatally, it is unknown whether cocaine d irectly activates the embryonic HPA axis or if 5-HT2 receptors are involved . Domestic chicken eggs with viable embryos were exposed to either the 5-HT 2 receptor agonist dimethoxyiodophenylaminopropane (DOI: 0.4, 0.8, or 1.2 m g/kg egg) or saline on embryonic day 18 (Els). In a second study, the 5-HT2 antagonist ritanserin (0.3 mg/kg egg, a dose found effective against other effects of DOI or cocaine) or vehicle was administered on E17, prior to tr eatment on E18 with either saline or cocaine (5 injections of 12 mg/kg egg, equivalent to a total dose of 3.5 mg/egg). Radioimmunoassay was used to me asure serum corticosterone from blood samples taken approximately 1-2 h aft er drug injections. DOI significantly raised corticosterone in a dose-relat ed fashion. Cocaine-induced corticosterone elevations were blocked by pretr eatment with ritanserin, whereas ritanserin by itself did not affect cortic osterone concentrations. These data indicate that 5-HT2 receptors are invol ved in cocaine's effect on the HPA axis during late chicken embryogenesis. (C) 2001 Elsevier Science Inc. All rights reserved.