MUSCARINIC CHOLINERGIC RECEPTOR REGULATION AND ACETYLCHOLINESTERASE INHIBITION IN RESPONSE TO INSECTICIDE EXPOSURE DURING DEVELOPMENT

Neonatal rats were exposed to parathion, an acetylcholinesterase inhib iting organophosphorus pesticide, during a rapid phase of cholinergic receptor development. Rats were given subcutaneous injections of 1.5 m g/kg/day from postnatal days 8-20. The immediate effects of subchronic developmental exposure were assessed in 21-day-old animals and more p ersistent effects assessed in 36-day-old animals. There was a 61% inhi bition of acetylcholinesterase and a 27% decrease of muscarinic recept or density in 21-day-old treated rats. The reduction in receptor densi ty was dose-dependent and a significant correlation was found between the level of acetylcholinesterase inhibition produced by parathion and the reduction in receptor density. It was estimated that a minimum of at least 15% prolonged inhibition of forebrain acetylcholinesterase b y parathion was necessary to reduce receptor density. Regional analyse s of receptor autoradiograms of 21-day-old animals indicated muscarini c receptors in the cortex and hippocampus were preferentially lost. Th e anterior thalamus was notable in having a high density of cholinergi c receptors which were unaffected by parathion treatment. No changes w ere found in the affinity of [H-3]QNB for the receptor or in the bindi ng of the agonist, acetylcholine, in competition binding studies. AChE activity and muscarinic receptor density returned to normal after a 1 6 day recovery period. Parathion treated animals were growth inhibited but, growth retardation induced by undernutrition did not alter recep tor density or affinity of QNB for muscarinic receptors. Thus, the tra nsient decrease in receptor density in parathion exposed animals was s imilar to the response previously observed in adults and was not secon dary to growth retardation or undernutrition. Receptor densities and a cetylcholinesterase levels were regulated back to normal values after a 16 day recovery period in spite of the perturbation of cholinergic f unction during cholinergic synapse and receptor development.