title: Effect of histamine on muscimol-induced working memory deficits in radial maze performance.
abstract: We investigated the participation of gamma-aminobutyric acid (GABA) neurons of the medial septal area in eight-arm radial maze performance in rats. The intra-septal injection of muscimol, a GABA(A) agonist, caused an increase in total error and working memory error. On the other hand, no significant effect was observed with reference memory error. Donepezil and tacrine (cholinesterase inhibitors) antagonized the muscimol-induced spatial memory deficits. Histidine (1500 mg/kg, i.p.) also improved the total error and working memory error induced by muscimol. At this dose, histidine caused a significant increase in the histamine content of the cortex, hippocampus, and hypothalamus in rats. In addition, the intra-hippocampal injection of histamine also antagonized muscimol-induced spatial memory deficits. The practical conclusion is that the GABA(A) receptor of the medial septal area plays an important role in working memory, and also, the disturbance of working memory induced by muscimol is mediated not only by cholinergic but also by histaminergic systems in the spatial memory of rats.
authors.affiliation: Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8530, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Azusa
authors.initials: A
authors.lastname: Mikami
authors.forename: Yoko
authors.initials: Y
authors.lastname: Fujii
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kamei
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000633:toxicity*; D058785:GABA-A Receptor Agonists; D006632:Histamine / Q000378:metabolism / Q000494:pharmacology*; D006639:Histidine / Q000494:pharmacology; D007189:Indans / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced* / Q000523:psychology*; D008570:Memory, Short-Term / Q000187:drug effects; D008845:Microinjections; D009118:Muscimol / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D013619:Tacrine / Q000494:pharmacology
chemical_list: D002800:Cholinesterase Inhibitors; D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D007189:Indans; D010880:Piperidines; D009118:Muscimol; D006639:Histidine; D013619:Tacrine; D006632:Histamine; D000077265:Donepezil