KAINIC ACID-INDUCED GENERALIZED SEIZURES ALTER THE REGIONAL HIPPOCAMPAL EXPRESSION OF THE RAT M1 AND M3 MUSCARINIC ACETYLCHOLINE-RECEPTOR GENES

We investigated the gene expression responses using in situ hybridizat ion with radiolabelled riboprobes for the mi and m3 subtypes of muscar inic cholinergic receptors in the rat hippocampus following a brief (5 -min) kainic acid-induced behavioral seizure. The kainic acid was intr aperitoneally administered, and the ensuing generalized convulsive sei zure terminated with diazepam. Our results demonstrate that the expres sion of the mi subtype was significantly reduced in the CA1, CA3 and t he dentate granule cells by 3 h after the administration of kainic aci d, while no significant change was observed in any hippocampal subfiel d for the m3 subtype. By 6 h post challenge, the mi subtype was still decreased in all hippocampal subfields examined, while the m3 subtype remained unchanged from vehicle injected control. At 24 h post challen ge, both the m1 and m3 subtypes were significantly reduced in the CA1 and CA3 subfields; the expression of the mi subtype in the dentate gra nule cells, however, had recovered to levels indistinguishable from ve hicle-injected control. These results demonstrate that epileptiform ac tivity induced by kainic acid administration promotes alterations in t he expression levels for both the mi and m3 muscarinic receptor genes, and suggest that the activity of this neuromodulatory system in the h ippocampus may be altered through activity-dependent mechanisms at ear ly times following seizures. (C) 1997 Elsevier Science B.V.