title: Effects of antipsychotic medication on muscarinic M1 receptor mRNA expression in the rat brain.
abstract: Alterations in muscarinic M1 receptor protein and mRNA expression have been revealed in post-mortem brains of schizophrenia patients. Most patients had been treated with antipsychotics, so medication effects cannot be excluded as a possible explanation for these results. With in situ hybridization, this study investigated M1 receptor mRNA expression in rats treated with the typical antipsychotic haloperidol (0.3 mg/kg/day) and the atypical antipsychotics olanzapine (1.5 mg/kg/day) and aripiprazole (2.25 mg/kg/day) for 1 or 12 weeks. Compared with the control group, haloperidol significantly increased (approximately 13-21%, P < 0.05) M1 mRNA expression in the CA1, CA2, and CA3 regions of the hippocampus after both 1 and 12 weeks of treatment, and it also increased (approximately 17%, P < 0.01) M1 mRNA expression in the substantia nigra compacta after 1 week of treatment. Olanzapine significantly increased (14-22%, P < 0.05) M1 mRNA expression in the hippocampus (CA1, CA2, and CA3) and substantia nigra compacta after 12 weeks of treatment, but not after 1 week. Aripiprazole significantly increased (17%, P < 0.01) M1 mRNA expression in the hippocampus (CA1) after both 1 and 12 week treatments and increased (12%, P < 0.05) M1 mRNA expression in the nucleus accumbens after 1 week of treatment. Despite their different affinities for muscarinic M1 receptors, all three antipsychotic medications induced a similar trend of change in M1 mRNA expression in selected brain regions. These data suggest that the decreased M1 receptor protein and mRNA expression observed in schizophrenia patients is unlikely to be a consequence of drug treatments and implicates muscarinic M1 receptors in the pharmacotherapy of the disease.
authors.affiliation: Neurobiology Research Centre for Metabolic and Psychiatric Disorders, School of Health Sciences, University of Wollongong, Wollongong, New South Wales, Australia.
authors.forename: Mei
authors.initials: M
authors.lastname: Han
authors.forename: Kelly
authors.initials: K
authors.lastname: Newell
authors.forename: Katerina
authors.initials: K
authors.lastname: Zavitsanou
authors.forename: Chao
authors.initials: C
authors.lastname: Deng
authors.forename: Xu-Feng
authors.initials: XF
authors.lastname: Huang
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D000068180:Aripiprazole; D001569:Benzodiazepines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D017403:In Situ Hybridization; D000077152:Olanzapine; D010879:Piperazines / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043643:Receptor, Muscarinic M1 / Q000096:biosynthesis* / Q000187:drug effects*; D013995:Time