The non-competitive AMPA receptor antagonist (GYKI 52466) blocks quisqualate-induced acetylcholine release from the rat hippocampus and striatum: an in vivo microdialysis study.
The effects of the non-N-methyl-D-aspartate (NMDA) agonist quisqualate (QUIS) and selective AMPA/kainate receptor antagonist 1-(aminophenyl)-methyl-7, 8-methyilendioxy-5H-2,3-benzodiazepine (GYKI 52466) on the release of acetylcholine (ACh) from the hippocampus and striatum of freely moving rats were studied by transversal microdialysis. Acetylcholine level in the dialisate was measured by the high performance liquid chromatography (HPLC) method with an electrochemical detector. The QUIS (100 microM) perfused through the striatum induced an increase of extracellular ACh level (250%) which lasted for over 1h and gradually returned to basal values. Local perfusion of GYKI 52466 (10-100 microM) to the striatum did not change the basal release of ACh. GYKI 52466 (10 microM) administered together with QUIS (100 microM) in he striatum antagonized the stimulant effect of QUIS on the ACh release. Local administration of the QUIS (100 microM) through the microdialysis fiber implanted in the hippocampus, caused a long lasting increase of extracellular hippocampal ACh level (360%) which was reversed when the drug was withdrawn from the perfusion solution. The stimulant effect of QUIS was antagonized by concomitant perfusion of GYKI (10 microM). No effect was seen on the basal ACh release when GYKI (10-100 microM) was perfused through the hippocampus. Local perfusion with tetrodotoxin (1 microM) decrease the basal release of ACh and prevented the QUIS-induced increase of ACh both in the hippocampus and striatum. Our in vivo neurochemical results indicate that hippocampal and striatal cholinergic systems are regulated by non-NMDA (probably AMPA) glutamatergic receptors located in the hippocampus and striatum.
Rakovska
Angelina
A
Institute of Physiology, Bulgarian Academy of Sciences, Acad. G. Bonchev St., bl. 23, 1113 Sofia, Bulgaria. rakovska@bio25.bas.bg
Kiss
Janos P
JP
Raichev
Peter
P
Lazarova
Maria
M
Kalfin
Reni
R
Djambazova
Elena
E
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001569:Benzodiazepines; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D016318:Quisqualic Acid / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D013779:Tetrodotoxin / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; C061950:GYKI 52466; D001569:Benzodiazepines; D013779:Tetrodotoxin; D016318:Quisqualic Acid; D000109:Acetylcholine