Microarray analysis reveals distinct gene expression patterns in the mouse cortex following chronic neuroleptic and stimulant treatment: implications for body weight changes.

Abstract

Atypical neuroleptics are associated with clinical significant weight gain, whereas stimulants are used as anorexiant drugs. The aim of this study was to examine gene expression changes in the mouse frontal cortex following chronic oral treatment with antipsychotics and a stimulant by microarray assessments. Twenty 10-12-week-old male C57BL6 mice received daily for 31 days either the typical neuroleptic haloperidol (1 mg/kg), the atypical neuroleptic clozapine (10 mg/kg) or the stimulant phenylpropanolamine (3 mg/kg). We identified a set of genes that was differently expressed between the neuroleptic-treated groups and the stimulant-treated group. Importantly, we found in the majority of gene alterations down-regulation in genes involved in ATP biosynthesis and lipid metabolism following the stimulant treatment, suggesting these genes as candidates that may regulate body weight. We also identified remarkable expression patterns of genes that encode signalling molecules (e.g. insulin, mitochondrial uncoupling protein 1) that are implicated in the control of food intake and are differently expressed in the neuroleptic groups.