The acetylcholine release enhancer linopirdine induces Fos in neocortex ofaged rats

Centrally acting cholinergic agents induce the immediate early gene c-fos i n the rat brain resulting in transient increases of Fos protein, most notab ly in the cerebral cortex. In this study we have monitored by Fos immunohis tochemistry the effect of the acetylcholine release enhancer linopirdine (D UP996) on the immediate early gene c-fos in brains of 3 months and 30 month s old rats. In young rats linopirdine had only a marginal effect on Fos exp ression. In contrast, in aged rats linopirdine caused widespread expression of Fos throughout neocortex. In somatosensory cortex, the induction of the c-fos gene by linopirdine was nearly completely blocked by atropine and sc opolamine and strongly attenuated by the NMDA receptor blockers CPP and MK- 801. The results suggest that the age-related decline in acetylcholine rele ase in rodents can be partially compensated for by administration of linopi rdine. (C) 2001 Elsevier Science Inc. All rights reserved.