A high-fat diet, but not haloperidol or olanzapine administration, increases activated microglial expression in the rat brain

Abstract

This study examined the effects of chronic treatment of the antipsychotic drugs, haloperidol and olanzapine, on microglial activation in the brain. In addition, we explored the interaction of these antipsychotic drugs with normal and high-fat diet. In order to measure activated microglial expression, we used [³H] PK11195 in vitro autoradiography. Male Sprague Dawley rats were given a diet of either regular chow diet or a high-fat diet, and assigned either water, haloperidol drinking solution (1.5 mg/kg), or olanzapine drinking solution (10 mg/kg) for four weeks. Following treatment, rats were euthanized and brains extracted for [³H] PK11195 autoradiography. Rats on 4 weeks of a high-fat diet showed increased [³H] PK11195 binding compared to rats on a normal diet in the temporal association cortex (19 %), ectorhinal cortex (17 %), entorhinal cortex (18 %), and perirhinal cortex (18 %), irrespective of drug treatment. These are regions associated with memory, sensory, and visual processing. Rats treated with either haloperidol or olanzapine showed no differences in [³H] PK11195 binding compared to the control group. However, there were differences between the 2 different antipsychotic medications themselves. Haloperidol increased [³H] PK11195 binding in the amygdala (23 %), ectorhinal cortex (24 %), and perihinal cortex (29 %), compared to olanzapine. These results corroborate a known role of a high-fat diet and central inflammatory changes but suggest no role of these antipsychotic drugs in promoting neuroinflammation across 4 weeks compared to normal control rats.

Keywords: Antipsychotic drugs; Autoradiography; Neuroinflammation; Obesity; Schizophrenia.