Chronic haloperidol treatment results in a decrease in the expression of myelin/oligodendrocyte-related genes in the mouse brain
Article first published online: 18 DEC 2006
Copyright © 2006 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 85, Issue 4, pages 757–765, March 2007
How to Cite
Narayan, S., Kass, K. E. and Thomas, E. A. (2007), Chronic haloperidol treatment results in a decrease in the expression of myelin/oligodendrocyte-related genes in the mouse brain. J. Neurosci. Res., 85: 757–765. doi: 10.1002/jnr.21161
- Issue published online: 14 FEB 2007
- Article first published online: 18 DEC 2006
- Manuscript Accepted: 31 OCT 2006
- Manuscript Revised: 13 OCT 2006
- Manuscript Received: 30 AUG 2006
- National Institutes of Health. Grant Numbers: NS44169, MH069696
- white matter;
Schizophrenia is a complex psychiatric illness that manifests as a combination of positive symptoms, negative symptoms, and cognitive deficits. Antipsychotic drugs, such as haloperidol, attenuate dopamine receptor signaling in neurons and constitute the frontline treatment for the positive symptoms of schizophrenia. However, haloperidol treatment has also been reported to exacerbate preexisting negative symptoms/cognitive deficits and the severity of these deficits has been correlated with white matter pathology in schizophrenia. Indeed, several studies implicate oligodendrocyte function in the pathophysiology of schizophrenia, but it is unknown whether these effects are related to drug treatment. It is well established that haloperidol alters gene expression in neurons. However, its effect on oligodendrocytes is unknown. In this study, we investigate the effects of chronic haloperidol treatment on the expression of eight genes known to play critical roles in myelin/oligodendrocyte function. We treated male mice with haloperidol (2 mg/kg/day) for 30 days and measured gene expression changes by using in situ hybridization analysis and quantitative densitometry. Haloperidol caused a decrease in the expression of these genes in several white matter regions of the mouse CNS. In contrast, clozapine (10 mg/kg/day) had no effect on the expression of a subset of these genes. This has important implications for both disease pathology and the consideration of treatment options for patients. © 2006 Wiley-Liss, Inc.