Haloperidol-induced changes in glutathione and energy metabolism: effect of nicergoline.

The aim of this study was to evaluate the possible effects of nicergoline, a semisynthetic ergot derivative, on the biochemical changes observed durin g chronic treatment with haloperidol in male Sprague-Dawley rats. Chronic t reatment with haloperidol induced a significant decrease in the cellular gl utathione (GSH) content in selected areas of the brain (cerebellum, striatu m and cortex) and in the liver. Prolonged nicergoline administration was ab le to antagonize the haloperidol-induced GSH decrease, maintaining the GSH concentration at levels comparable to those observed in the control group. Analysis of the energy charge revealed changes similar to those observed fo r GSH: haloperidol induced a significant decrease in ATP and energy charge that was completely reversed by repeated nicergoline administration. In con clusion, chronic treatment with the classical antipsychotic haloperidol ind uces profound biochemical changes in the brain and in the liver. Nicergolin e treatment is able to counteract the haloperidol-induced decrease in GSH l evels and energy charge, suggesting a potential role of the drug in the tre atment of neuroleptic-induced side effects. (C) 1999 Elsevier Science B.V. All rights reserved.