Embryonic cocaine exposure and corticosterone: serotonin(2) receptor mediation.
Cocaine activates the mature hypothalamic-pituitary-adrenal (HPA) axis, increasing corticosterone concentrations in animals and humans and serotonin(2) receptors (5-HT(2)) are involved in this effect. Although prenatal cocaine exposure is associated with altered responsiveness of the HPA axis to "stress" and serotonergic compounds postnatally, it is unknown whether cocaine directly activates the embryonic HPA axis or if 5-HT(2) 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 mg/kg egg) or saline on embryonic day 18 (E18). In a second study, the 5-HT(2) 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 treatment 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 measure serum corticosterone from blood samples taken approximately 1-2 h after drug injections. DOI significantly raised corticosterone in a dose-related fashion. Cocaine-induced corticosterone elevations were blocked by pretreatment with ritanserin, whereas ritanserin by itself did not affect corticosterone concentrations. These data indicate that 5-HT(2) receptors are involved in cocaine's effect on the HPA axis during late chicken embryogenesis.
Larson
E B
EB
Department of Pharmacology, University of Minnesota Medical School, 6-120 Jackson Hall, 321 Church Street Southeast, Minneapolis, MN 55455, USA.
Schrott
L M
LM
Bordone
L
L
Sparber
S B
SB
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D002642:Chick Embryo; D003042:Cocaine / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D009490:Neurosecretory Systems / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects*; D016713:Ritanserin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D000662:Amphetamines; D018765:Dopamine Uptake Inhibitors; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D016713:Ritanserin; D003042:Cocaine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D003345:Corticosterone