Effects of haloperidol on cell proliferation in the early postnatal rat brain

Abstract

Haloperidol, a widely used neuroleptic, produced a significant depression of the rate of [3H]thymidine incorporation into the DNA of 11-day-old rat brain. The reduction of in-vivo DNA synthesis rate was detectable by 4 h after subcutaneous injection of a single dose of haloperidol (20 mg/kg) and through the period 10-24 h after drug treatment the rate was less than 50% of that of controls in the forebrain. [3H]Thymidine incorporation returned to control values by 32 h. The effect on the cerebellum was similar but less pronounced. The depression was dose-dependent and a half-maximal effect was produced with haloperidol doses of 5-10 mg/kg. Parallel histological studies on treated rats suggested prolongation of the DNA synthesis phase of the cell cycle in the forebrain subependymal layer, associated with an increase in turnover time of about 15%.