Participation of cholinergic system in memory deficits induced by blockade of hippocampal mGlu(1) receptors.
We investigated the role of hippocampal group I metabotropic glutamate receptors (mGlu(1) receptors) in the retrieval process of spatial memory using 8-arm radial maze performance with 4 arms baited. In addition, the participation of the cholinergic system in memory deficits induced by mGlu(1) receptors antagonist was studied. Intrahippocampal injection of (R,S)-1-Aminoindan-1,5-dicarboxylic acid (AIDA), a mGlu(1) receptor antagonist, significantly increased total error, reference memory error and working memory error at a dose of 20 nmol/side. Donepezil (0.5 and 1.0 mg/kg, p.o.) showed an ameliorative effect on AIDA-induced memory deficits. Improvement by donepezil of AIDA-induced memory deficits was antagonized by scopolamine (5 nmol/side) but not by mecamylamine (200 nmol/side) at a dose that did not affect performance. These findings clearly indicate that hippocampal mGlu(1) receptors play an important role in the retrieval of spatial memory. Furthermore, we found that hippocampal mGlu(1) receptors were closely associated with muscarinic receptors in memory performance.
Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Azusa
A
Mikami
Takayoshi
T
Masuoka
Masa
M
Yasuda
Yasuko
Y
Yamamoto
Chiaki
C
Kamei
D000818:Animals; D018678:Cholinergic Agents / Q000494:pharmacology*; D018680:Cholinergic Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007189:Indans / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D018782:Maze Learning; D008464:Mecamylamine / Q000494:pharmacology / Q000627:therapeutic use; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000187:drug effects*; D012601:Scopolamine / Q000494:pharmacology / Q000627:therapeutic use
C095756:1-aminoindan-1,5-dicarboxylic acid; D018678:Cholinergic Agents; D018680:Cholinergic Antagonists; D002800:Cholinesterase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D007189:Indans; D010880:Piperidines; D018094:Receptors, Metabotropic Glutamate; D008464:Mecamylamine; D000077265:Donepezil; D012601:Scopolamine