N-tert-butyl-alpha-phenylnitrone, a free radical scavenger with anticholinesterase activity does not improve the cognitive performance of scopolamine-challenged rats

Reversible inhibitors of acetylcholinesterase improve spatial learning and memory in animal models of cognitive impairment. Here we investigate if the beneficial effects of Free radical scavenger N-tert-butyl-alpha-phenylnitr one (PBN) on cognitive performance could be explained by its recently disco vered anticholinesterase activity. Morris water maze experiment was perform ed to examine the effect of PBN on the impairment of spatial learning and m emory induced by the antagonist of cholinergic muscarinic transmission scop olamine. In situ hybridization histochemistry experiment was performed to s tudy its effects on the induction of immediate early gene expression (c-fos , c-jun) by dopamine D1 receptor agonist SKF-82958 and on the augmentation of the SKF-83958-induced expression of these genes by scopolamine. In both experiments. the effects of PEN were compared to the effects of reversible anticholinesterase physostigmine. We found that physostigmine but not PEN s ignificantly, reversed the cognitive impairment in scopolamine-challenged r ats, prevented the induction of c-fos and c-jun mRNAs by SKF-82958 and atte nuated the augmentation of the SKF-87958-induced expression of these genes by scopolamine. The present experiments did not reveal a significant in viv o anticholinesterase activity of PEN. (C) 2001 ISDN. Published by Elsevier Science Ltd. All rights reserved.