Modulation of M1 and M2 muscarinic receptor subtypes following repeated organophosphate exposure in rats

Repeated exposure to organophosphates has been shown to cause a decrease in muscarinic cholinergic receptors in the central and peripheral nervous system. The present study measured the modulation of M1 and M2 muscarinic receptor subtypes in rat brain areas during and following a 2-week daily exposure to the organophosphate disulfoton. The radioligands [3H]telenzepine and [3H]AFDX 384 were utilized to label M1 and M2 receptors, respectively. The study found comparable down-regulation in both [3H]telenzepine- and [3H]AFDX 384-labeled receptors in cortex, hippocampus, and striatum during exposure. Recovery of M2 subtype was slower than recovery of M1, especially in the hippocampus. The results suggest that M1 and M2 receptor subtypes may be similarly regulated in response to subchronic exposure to organophosphates, but that recovery of receptor subtypes to control levels may be governed by distinct factors.