title: Differential effects of 5-HT3 receptor antagonism on working memory failure due to deficiency of hippocampal cholinergic and glutamatergic transmission in rats.
abstract: The muscarinic acetylcholine receptor antagonist scopolamine significantly increased the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) in the working memory task with a three-panel runway setup, when injected bilaterally at 3.2 microg/side into the dorsal hippocampus. Concurrent infusion of the selective and potent 5-hydroxytryptamine3 (5-HT3) receptor antagonist Y-25130 (0.32 and 1.0 microg/side) significantly attenuated the increase in working memory errors induced by intrahippocampal 3.2 microg/side scopolamine. Intrahippocampal Y-25130 (1.0 microg/side) by itself did not affect working memory errors. On the other hand, intrahippocampal administration of the competitive NMDA receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) at 32 ng/side caused a significant increase in the number of working memory errors. However, Y-25130 at 1.0 microg/side did not affect the increase in working memory errors when infused intrahippocampally together with 32 ng/side CPP. These results suggest that antagonism of hippocampal 5-HT3 receptors is ineffective against working memory failure resulting from blockade of NMDA receptor-mediated neurotransmission, but that it can compensate deficiency of septohippocampal cholinergic activity involved in working memory function of rats.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ohno
authors.forename: S
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010078:Oxazines / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors; D011985:Receptors, Serotonin / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3; D012601:Scopolamine / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D018691:Excitatory Amino Acid Antagonists; D018727:Muscarinic Antagonists; D010078:Oxazines; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D018698:Glutamic Acid; C070671:azasetron; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D012601:Scopolamine; D000109:Acetylcholine