Thermoregulatory effects of chlorpyrifos in the rat: long-term changes in cholinergic and noradrenergic sensitivity.
Subcutaneous injection of a sublethal dose of chlorpyrifos (CHLP), an organophosphate (OP) pesticide, causes long-term inhibition in cholinesterase activity (ChE) of brain, blood, and other tissues. Such prolonged inhibition in ChE should lead to marked behavioral and autonomic thermoregulatory patterns, especially in terms of altered noradrenergic and cholinergic sensitivity. To evaluate the behavioral and autonomic effects of long-term ChE inhibition, Long-Evans rats were implanted with radiotelemetry transmitters that continuously monitored core temperature (Tc), heart rate (HR), and motor activity (MA). These parameters were monitored for 7 days following a single injection of peanut oil (vehicle control) or 280 mg/kg CHLP. CHLP led to a significant reduction in Tc during the first night after treatment but had no other effects on Tc. CHLP also resulted in a significant elevation in HR which lasted for approximately 72 h. Motor activity was unaffected by CHLP. Cholinergic and noradrenergic drug sensitivity was assessed between 7 and 25 days after CHLP. CHLP-treated rats were more sensitive to norepinephrine as based on a greater hyperthermic response. MA of CHLP-treated rats was more sensitive to scopolamine. On the other hand, the hypothermic effects of oxotremorine (0.4 mg/kg) were nearly abolished by CHLP treatment, indicating tolerance to cholinergic stimulation. The tachycardic effects of methyscopolamine were also greater in the CHLP group. Overall, the acute effects of CHLP are unusual compared to other OP's in that there is no hypothermic response, an attenuated nocturnal elevation in Tc and a prolonged elevation in HR.(ABSTRACT TRUNCATED AT 250 WORDS)
Gordon
C J
CJ
Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D004390:Chlorpyrifos / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D002802:Cholinesterases / Q000097:blood / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D019832:N-Methylscopolamine; D009638:Norepinephrine / Q000494:pharmacology*; D010095:Oxotremorine / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D010276:Parasympatholytics / Q000494:pharmacology; D051381:Rats; D012602:Scopolamine Derivatives / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects*
D002800:Cholinesterase Inhibitors; D010276:Parasympatholytics; D012602:Scopolamine Derivatives; D010095:Oxotremorine; D002802:Cholinesterases; D004390:Chlorpyrifos; D019832:N-Methylscopolamine; D009638:Norepinephrine