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.