Pharmacological evaluation of central adrenergic involvement in chlordecone-induced hypothermia.
Adrenergic involvement in the hypothermia produced by systemically administered chlordecone (CLD) was evaluated in the rat using intracisternal pretreatment with 6-hydroxydopamine (6-OHDA), alpha-adrenergic receptor antagonists (phenoxybenzamine and phentolamine) and beta-adrenergic antagonists (propranolol and atenolol). The effect of intraperitoneal administration of 75 mg/kg of chlordecone on colonic temperature (Tcol) in male Fischer-344 rats was measured 7 days after administration of 6-OHDA and 30 min following pretreatment with the receptor antagonists. Prior depletion of catecholamines in brain with 250 micrograms of 6-OHDA administered intracerebrally attenuated hypothermia induced by chlordecone, without affecting basal Tcol. Phenoxybenzamine (10 or 20 micrograms) and phentolamine (5 or 10 micrograms) also reduced the hypothermic response to chlordecone. The beta-adrenergic receptor antagonists propranolol (50 or 100 micrograms) and atenolol (10 or 20 micrograms) did not attenuate chlordecone-induced hypothermia. These data suggest that the hypothermia induced by chlordecone is a result of alterations in central alpha-adrenergic functions, possibly involved with the sympathetic control of vasomotor tone.
Cook
L L
LL
Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Edens
F W
FW
Tilson
H A
HA
D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D007631:Chlordecone / Q000494:pharmacology*; D002946:Cisterna Magna; D003106:Colon / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D004347:Drug Interactions; D006892:Hydroxydopamines / Q000494:pharmacology; D007036:Hypothermia, Induced; D007267:Injections; D007306:Insecticides / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine; D010643:Phenoxybenzamine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011941:Receptors, Adrenergic / Q000187:drug effects*
D006892:Hydroxydopamines; D007306:Insecticides; D011941:Receptors, Adrenergic; D010643:Phenoxybenzamine; D001262:Atenolol; D016627:Oxidopamine; D011433:Propranolol; D007631:Chlordecone; D004298:Dopamine; D009638:Norepinephrine; D010646:Phentolamine