INTERACTION OF CHLORPHENVINPHOS WITH CHOLINERGIC RECEPTORS IN THE RABBIT HYPOTHALAMUS

The purpose of this study was to find out whether chlorphenvinphos (CV P), an organophosphorous pesticide, interacts with the muscarinic chol inergic receptors in CNS. To attain this goal, the effects of intrahyp othalamic injections of oxotremorine (Ox), a muscarinic agonist, and p hysostigmine (Phys), a carbamate anticholinesterase, were compared wit h those produced by intrahypothalamic injections of CVP in the rabbit. It was found that the infusion of Ox (20 mu g) as well as Phys (200 m u g) into the anterior hypothalamus leads to an increase in the 4-7 Hz theta rhythm in the hippocampus and to the appearance of behavioral s ymptoms suggestive of a threat response. In the case of Ox, the effect s could be prevented by injections of 20 mu g scopolamine, a muscarini c antagonist. Pretreatment of the hypothalamus with 100 mu g hemicholi nium (HC-3) did not prevent the effects of Phys injected 2 h later. (H C-3 prevents the resynthesis of acetylcholine by blocking choline reup take. This leads to a gradual depletion of ACh stores and to an inhibi tion of the cholinergic transmission). It suggests that Phys activates directly postsynaptic muscarinic receptors. Intrahypothalamic injecti ons of CVP in doses of up to 1360 mu g produced no overt changes in be havior nor in the hippocampal EEG of the rabbit and did not prevent th e effect of subsequent injections of Ox. This suggests that CVP is nei ther an agonist nor antagonist of the muscarinic receptors in the rabb it hypothalamus.