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THE MUSCARINIC ANTAGONIST SCOPOLAMINE ATTENUATES CHLORPYRIFOS INDUCED HYPOTHERMIA IN THE DEVELOPING RAT.
Citation:
Mack, C M. AND C J. Gordon. THE MUSCARINIC ANTAGONIST SCOPOLAMINE ATTENUATES CHLORPYRIFOS INDUCED HYPOTHERMIA IN THE DEVELOPING RAT. Presented at Experimental Biology 2002, New Orleans, LA, 4/20-24/2002.
Description:
Chlorpyrifos (CHP), an anticholinesterase organophosphate (OP) pesticide, induces acute hypothermia in adult and developing rats. Previously we demonstrated that thermoregulation in preweanling pups is markedly more sensitive to the neurotoxic effects of CHP than in adults. The current study investigated whether or not CHP-induced hypothermia in pups is directly mediated via a cholinergic pathway. Male rats (Long-Evans), 13 d of age, were implanted with radio transmitters (Data Sciences, Inc.) to record core body temperature (Tc) and motor activity (MA). On day 17 rats were dosed with 15 mg/kg CHP or the corn oil (CO) vehicle (po), followed immediately by 0.5 mg/kg scopolamine (SCO) or saline (S) (ip). Pups treated with 15 mg/kg CHP/S experienced a rapid decrease in Tc (-2.6 0C) that recovered within 16 hr. Conversely, Tc of CHP/SCO treated rats was initially unaffected but decreased by -1.2 0C 6 hrs after injection. CHP/S significantly suppressed MA over the 24 hrs post dose. Pups receiving CHP/SCO were hyperactive (6 hrs) post dose, followed by a period of suppressed activity that recovered by 17 hrs post dose. Overall, SCO attenuated the effects of CHP on Tc and MA. These results suggest the neurotoxic effects of CHP on thermoregulation in developing rats involve stimulation of muscarinic cholinergic pathways.
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