Decreased M1 muscarinic receptor density in rat amphetamine model of schizophrenia is normalized by clozapine, but not haloperidol

Adi Malkoff, Avraham Weizman, Illana Gozes, Moshe Rehavi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

There is increasing evidence supporting the involvement of the muscarinic-cholinergic system in schizophrenia. We examined the M1 muscarinic receptor density and mRNA expression in brains of a rat amphetamine model of schizophrenia. We also assessed the effect of the model and chronic treatment with haloperidol and clozapine on brain M1 receptor density and gene expression. A significant decrease of about 20% in the density of M1 receptor was detected in the cortex and in the striatum of amphetamine model rats. A significant increase of 33% in the density of the M1 receptor was found in the cortex and striatum of rats treated chronically with clozapine (0.5 mg/kg), but not with haloperidol (25 mg/kg). Chronic clozapine, but not haloperidol, normalized the decrease in M1 receptors observed in amphetamine model rats, in both cortex and striatum. Regulation of the M1 receptor may occur in a post-transcriptional phase. Our findings suggest involvement of both dopaminergic and cholinergic-muscarinic systems in the pathophysiology and pharmacotherapy of schizophrenia.

Original languageEnglish
Pages (from-to)1563-1571
Number of pages9
JournalJournal of Neural Transmission
Volume115
Issue number11
DOIs
StatePublished - Nov 2008

Keywords

  • Acetylcholine
  • Amphetamine
  • Clozapine
  • Haloperidol
  • Pirenzepine
  • Schizophrenia

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