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Chronic phencyclidine (PCP)-induced modulation of muscarinic receptor mRNAs in rat brain : impact of antipsychotic drug treatment

Steward, Lucinda J and Kennedy, Matthew D and Morris, Brian J and Pratt, Judith A (2012) Chronic phencyclidine (PCP)-induced modulation of muscarinic receptor mRNAs in rat brain : impact of antipsychotic drug treatment. Neuropharmacology, 62 (3). pp. 1554-1563.

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Abstract

Many antipsychotics (APDs) have a high affinity for muscarinic receptors, which is thought to contribute to their therapeutic efficacy, or side effect profile. In order to define how muscarinic receptor gene expression is affected by atypical or typical APDs, rats were treated with chronic (2.58 mg/kg) PCP (a psychotomimetic) or vehicle, plus clozapine (20 mg/kg/day) or haloperidol (1 mg/kg/day), and M1, M2 and M3 receptor mRNA levels were determined in brain sections. Negligible changes in M2 or M3 muscarinic mRNA were detected in any region after clozapine or haloperidol. Chronic PCP administration increased M1 mRNA expression in the prefrontal cortex, which was not reversed by either chronic clozapine or haloperidol treatment. Chronic clozapine treatment in combination with PCP treatment decreased M1 receptor mRNA levels in the nucleus accumbens core, whereas chronic haloperidol in combination with PCP treatment increased M1 receptor mRNA levels in the ventromedial hypothalamus and medial amygdala. Thus M1 receptor gene expression is targeted by APDs, although the regions affected differ according to the APD treatment and whether PCP has been administered. The different brain circuitry modulated, may reflect the differing modes of action of typical and atypical APDs. These data provide support for the dysregulation of M1 receptors in schizophrenia, and furthermore, modulation by antipsychotic agents in the treatment of schizophrenia. This article is part of a Special Issue entitled 'Schizophrenia'.

Item type: Article
ID code: 32634
Notes: Copyright © 2011 Elsevier Ltd. All rights reserved.
Keywords: muscarinic receptor , antipsychotic drug treatment, M1 receptor, M2 receptor, M3 receptor, schizophrenia, clozapine, chronic phencyclidine, mRNAs, rat brain, impact, muscarinic receptor, Therapeutics. Pharmacology, Cellular and Molecular Neuroscience, Pharmacology
Subjects: Medicine > Therapeutics. Pharmacology
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
Depositing user: Pure Administrator
Date Deposited: 19 Aug 2011 21:05
Last modified: 27 Mar 2014 09:30
URI: http://strathprints.strath.ac.uk/id/eprint/32634

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