Differential expression of GABA(A) receptor subunit mRNAs and ligand binding sites in rat brain following phencyclidine administration

Recent biochemical observations have suggested the abnormalities in the gam ma-amino-butyric acid (GABA)ergic system in schizophrenic brains. In the pr esent study, we investigated the subunits gene expressions and ligand bindi ng of the GABA(A) receptor following acute and chronic administration of ph encyclidine (PCP), which induces schizophrenia-like symptoms, in rats using in situ hybridization and in vitro quantitative autoradiography. PCF i.p. administration at a daily dose of 7.5 mg/kg resulted in a significant decre ase in expression of alpha 1 subunit mRNA in cerebral cortices (cingulate ( -13%) and temporal cortex (-6%)) and hippocampal formation (CA1 (-11%), CA2 (-10%), CA3 (-11%) and dentate gyrus (-1.2%)) 1 h after a single treatment . In the repeated PCP administrations for 14 days, the expression of beta 2 mRNA in the cerebellum (-10%) and of beta 3 mRNA in the cerebral cortices (cingulate (-12%), parietal (-16%) and temporal cortex (-16%), caudate puta men (-18%), inferior colliculus (-18%), and cerebellum (-15%) were signific antly decreased. In addition, [S-35] t-butylbicyclophosphorothionate (TBPS) binding was also reduced in layer IV of the frontoparietal cortex (-14%), inferior colliculus (-17%), and cerebellum (-12%) following chronic PCP tre atment, while no changes were observed following acute PCP treatment. These results indicate that single and repeated administrations of PCP independe ntly regulate the expression of GABA(A)/benzodiazepine (BZD) receptor subun its mRNA and its receptor binding in the brain. Synapse 38:51-60, 2000. (C) 2000 Wiley-Liss, Inc.