Crucial role of kainate receptors in mediating striatal kainate injection-induced decrease in acetylcholine M-1 receptor binding in rat forebrain

We investigated the roles of kainate-, alpha -amino-3-hydroxy-5-methylisoxa zol-4-propionate (AMPA)- and N-methyl-D-aspartate (NMDA)-receptors in media ting striatal kainate injection-induced decrease in the binding of acetylch oline M-1 receptors in rat forebrain. After unilateral intrastriatal inject ion of kainate (4 nmol), the bindings of [H-3]kainate (10 nM), [H-3]MK-801 (4 nM) and [H-3]pirenzepine (4 nM) to the rat ipsilateral forebrain membran es declined, reaching the lowest on day 2 to 4 and recovering on day 8. Sat uration binding studies, performed on day 2 post-injection, showed that kai nate (1, 2, 4 nmol) dose-dependently decreased B-max and K-d of the three l igands. (+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (M K-801), a selective NMDA receptor channel blocker, antagonised (from a dose of 4 nmol) kainate-induced decreases in the bindings of [H-3]kainate (up t o similar to 20%), [H-3]MK-801 (up to similar to 90%) and [H-3]pirenzepine (up to similar to 70%). In contrast, 6-cyano-7-nitroquinoxaline-2,3-dione ( CNQX), a selective non-NMDA receptor antagonist, almost completely abolishe d (from a dose of 12 nmol) kainate-induced decreases in the bindings of all the three ligands (up to similar to 95-98%). Cyclothiazide, a selective po tentiator that enhances AMPA receptor-mediated responses, significantly enh anced (from a dose of 4 nmol) kainate-induced decrease in the binding of [H -3]kainate but not that of [H-3]pirenzepine or [H-3]MK-801. In summary, the se results indicate that striatal kainate injection-induced decrease in the binding of acetylcholine M-1 receptors in rat forebrain is dependent on ac tivation of kainate receptors and, to a certain extent, a consequent involv ement of NMDA receptors. These and previous studies provide some evidence s howing that kainate receptors might play a crucial role in regulating excit atory amino acids (EAA)-modulated cholinergic neurotransmission in the cent ral nervous system (CNS). (C) 2000 Elsevier Science B.V. All rights reserve d.