title: The acetylcholine release enhancer linopirdine induces Fos in neocortex of aged rats.
abstract: Centrally acting cholinergic agents induce the immediate early gene c-fos in the rat brain resulting in transient increases of Fos protein, most notably in the cerebral cortex. In this study we have monitored by Fos immunohistochemistry the effect of the acetylcholine release enhancer linopirdine (DUP996) on the immediate early gene c-fos in brains of 3 months and 30 months old rats. In young rats linopirdine had only a marginal effect on Fos expression. 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 scopolamine and strongly attenuated by the NMDA receptor blockers CPP and MK-801. The results suggest that the age-related decline in acetylcholine release in rodents can be partially compensated for by administration of linopirdine.
authors.affiliation: The DuPont Pharmaceuticals Company, Wilmington, Delaware 19880-0400, USA.
authors.forename: G W
authors.initials: GW
authors.lastname: Dent
authors.forename: B L
authors.initials: BL
authors.lastname: Rule
authors.forename: Y
authors.initials: Y
authors.lastname: Zhan
authors.forename: R
authors.initials: R
authors.lastname: Grzanna
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000375:Aging / Q000502:physiology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D019579:Neocortex / Q000187:drug effects* / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D012601:Scopolamine / Q000494:pharmacology; D013003:Somatosensory Cortex / Q000187:drug effects / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007211:Indoles; D018727:Muscarinic Antagonists; D010879:Piperazines; D016760:Proto-Oncogene Proteins c-fos; D011725:Pyridines; D016291:Dizocilpine Maleate; D001285:Atropine; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D012601:Scopolamine; C061017:linopirdine; D000109:Acetylcholine