REDUCED BINDING OF (QUINUCLIDINYL-H-3 BENZILATE ASSOCIATED WITH CHRONICALLY LOW ACETYLCHOLINESTERASE ACTIVITY

(3H)-Quinuclidinyl benzilate (QNB) binding was examined in the cortex, striatum and hippocampus of rats repeatedly exposed to the anticholinesterase, diisopropyl fluorophosphate (DFP). Compared to vehicle-treated controls, a reduction in maximal binding of 25-30% was observed in these brain regions. The reduction in binding was associated with regional acetylcholinesterase (AChE) inhibition of 80-90%. A tendency of lower muscarinic acetylcholine receptor (m-AChR) affinity for (3H)-QNB in control preparations, compared to those from DFP-treated rats, was observed. However, only in the case of the striatal control homogenate was there a significant increase in apparent KD. A concomitant feature of chronically low AChE activity is therefore a reduction, mainly in number, of m-AChR's. These findings support the hypothesis that in the central nervous system (CNS) DFP tolerance and cholinomimetic subsensitivity may involve the m-AChR. © 1979.