Gralewicz_1995_Neurotoxicol.Teratol_17_289

The purpose of this study was to find out whether chlorphenvinphos (CVP), an organophosphorous pesticide, interacts with the muscarinic cholinergic receptors in CNS. To attain this goal, the effects of intrahypothalamic injections of oxotremorine (Ox), a muscarinic agonist, and physostigmine (Phys), a carbamate anticholinesterase, were compared with those produced by intrahypothalamic injections of CVP in the rabbit. It was found that the infusion of Ox (20 micrograms) as well as Phys (200 micrograms) into the anterior hypothalamus leads to an increase in the 4-7 Hz theta rhythm in the hippocampus and to the appearance of behavioral symptoms suggestive of a threat response. In the case of Ox, the effects could be prevented by injections of 20 micrograms scopolamine, a muscarinic antagonist. Pretreatment of the hypothalamus with 100 micrograms hemicholinium (HC-3) did not prevent the effects of Phys injected 2 h later. (HC-3 prevents the resynthesis of acetylcholine by blocking choline reuptake. This leads to a gradual depletion of ACh stores and to an inhibition of the cholinergic transmission). It suggests that Phys activates directly postsynaptic muscarinic receptors. Intrahypothalamic injections of CVP in doses of up to 1360 micrograms produced no overt changes in behavior nor in the hippocampal EEG of the rabbit and did not prevent the effect of subsequent injections of Ox. This suggests that CVP is neither an agonist nor antagonist of the muscarinic receptors in the rabbit hypothalamus.