title: Intraseptal infusion of the cholinergic agonist carbachol impairs delayed-non-match-to-sample radial arm maze performance in the rat.
abstract: The medial septal nucleus regulates the physiology and emergent functions (e.g., memory formation) of the hippocampal formation. This nucleus is particularly rich in cholinergic receptors and is a putative target for the development of cholinomimetic cognitive enhancing drugs. A large number of studies have demonstrated that direct intraseptal drug infusions can produce amnestic or promnestic effects. While a few studies have examined the effects of direct intraseptal infusion of cholinomimetics on spatial memory performance (with drug "on-board" at the time of testing), the effects of post-acquisition infusions have not been assessed. We hypothesized that post-acquisition intraseptal infusion of cholinomimetics, by promoting hippocampal theta and suppressing the occurrence of hippocampal sharp waves, may disrupt the long-term retention and consolidation of memory. The present study examined the effects of intraseptal infusion of the cholinergic agonist carbachol in a delayed-non-match-to-sample radial maze task. Treatments were administered immediately following (within 1 min) the sample session with a retention session 2 h later. Carbachol infusions (12.5-125 ng in 0.5 microl) produced a linear dose-dependent decrease in correct entries and increase in retroactive errors, without any change in proactive errors or latency-per-choice. These findings suggest that post-acquisition intraseptal cholinergic treatments can produce amnesia. These findings are discussed with regard to multi-stage models of hippocampal-dependent memory formation and the further development of therapeutic strategies in the treatment of mild cognitive impairment as well as age-related cognitive decline and Alzheimer's dementia.
authors.affiliation: Department of Psychology, University of Connecticut, Storrs, Connecticut 06269, USA.
authors.forename: Jamie G
authors.initials: JG
authors.lastname: Bunce
authors.forename: Helen R
authors.initials: HR
authors.lastname: Sabolek
authors.forename: James J
authors.initials: JJ
authors.lastname: Chrobak
mesh_terms: D000818:Animals; D002217:Carbachol / Q000008:administration & dosage / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007263:Infusions, Parenteral; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects
chemical_list: D018679:Cholinergic Agonists; D002217:Carbachol