Blockade of 5-HT1A receptors compensates loss of hippocampal cholinergic neurotransmission involved in working memory of rats.
NAN-190, a selective 5-HT1A receptor antagonist, had no effect on 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 bilaterlly at 0.32 or 1.0 micrograms/side into the dorsal hippocampus. Intrahippocampal administration of the muscarinic receptor antagonist scopolamine at 3.2 micrograms/side or the competitive NMDA receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) at 32 ng/side significantly increased the number of working memory errors. The increase in working memory errors induced by intrahippocampal scopolamine (3.2 micrograms/side) was reduced by concurrent infusion of 0.32 and 1.0 microgram/side NAN-190, an effect that reached significance only for the 1.0 microgram/side dose. In contrast, NAN-190 at 1.0 micrograms/side did not affect the increase in working memory errors when infused intrahippocampally together with 32 ng/side CPP. These results suggest that blockade of hippocampal 5-HT1A receptors does not affect impairment of working memory resulting from block of NMDA receptor-mediated neurotransmission, but that it can compensate deficiency of septohippocampal cholinergic activity involved in working memory performance of rats.
Ohno
M
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University 62, Fukuoka, Japan.
Watanabe
S
S
D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects; D008845:Microinjections; D018721:Muscarinic Agonists / Q000494:pharmacology; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012601:Scopolamine / Q000008:administration & dosage / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*
D018691:Excitatory Amino Acid Antagonists; D018721:Muscarinic Agonists; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D012601:Scopolamine