Embryonic "binge" cocaine exposure alters neural-immune and neural-endocrine interactions in young chickens: involvement of serotonin(2) receptors.
As part of our characterization of the developmental consequences of prenatal cocaine exposure, cocaine was injected into eggs containing viable chicken embryos on embryonic day (E) 18 and the fever response to the endotoxin lipopolysaccharide (LPS) and a delayed-type hypersensitivity response to phytohemagglutinin (PHA) were assessed postnatally. E18 cocaine exposure did not affect basal body temperature. LPS induced a fever in the chicks at 4 h post-injection on post-hatch day (D) 4 and 2 h post-injection on D24. E18 cocaine exposure suppressed the peak LPS-induced fever by 50% at both ages. E18 cocaine exposure also suppressed the hypersensitivity reaction to an intradermal injection of PHA on D17, while having no effect on the response to a saline injection. To determine the importance of serotonin(2) (5-HT(2)) receptors in the developmental toxicity of cocaine, varying doses of the 5-HT(2) antagonist ritanserin were injected on E17 followed by cocaine on E18. Ritanserin, like cocaine, did not alter basal temperature, but it dose-relatedly attenuated or blocked cocaine's effect on LPS-induced fever on both D4 and D24. Ritanserin pretreatment was also able to block the blunted isolation stress response seen in D16 chicks following E18 cocaine exposure. Thus, late prenatal cocaine exposure significantly alters adaptive fever and hypersensitivity responses, and embryonic 5-HT(2) receptors played a mediating role in the fever effect.
Schrott
L M
LM
Department of Pharmacology, University of Minnesota Medical School, 6-120 Jackson Hall, 321 Church St. S.E., Minneapolis, MN 55455-0217, USA. schro041@tc.umn.edu
Sparber
S B
SB
D000818:Animals; D001491:Basophils / Q000276:immunology; D002642:Chick Embryo; D002645:Chickens; D003042:Cocaine / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005334:Fever / Q000139:chemically induced / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000276:immunology; D008070:Lipopolysaccharides; D015213:Neuroimmunomodulation / Q000187:drug effects*; D010835:Phytohemagglutinins; D011985:Receptors, Serotonin / Q000378:metabolism*; D016713:Ritanserin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D012934:Social Isolation; D013315:Stress, Psychological / Q000276:immunology
D018765:Dopamine Uptake Inhibitors; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D016713:Ritanserin; D003042:Cocaine; D003345:Corticosterone