Reduced binding of (3H)-quinuclidinyl 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 K_D. 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.