Enhancement of Memory by a Cholinesterase Inhibitor Associated with Muscarinic Receptor Down-regulation

Rats trained on a passive avoidance task 24 hours following a single intraperitoneal injection of diisopropyl fluorophosphate (DFP, 1.2 mg/kg) showed enhanced retention when tested 7 days later. In a parallel group of rats, reduced cortical [3H] quinuclidinyl benzilate binding was demonstrable 24 hours following DFP administration. The association of reduced muscarinic receptor binding and enhanced performance on a memory task contradicts previous reports which suggested that retention was impaired by treatments which down-regulate muscarinic receptors. This contradiction may be reconciled if pre-synaptic factors such as agonist availability are considered in conjunction with post-synaptic receptor effects.