Effect of amphetamine on the metabolism and incorporation of [3H]-thymidine into DNA of developing rat brain.

High doses of dl-amphetamine (15-40 mg/kg in free base, s.c.) inhibited the cell proliferation in the forebrain of 10-day-old rats 2 h after treatment, in terms of the incorporation of [3H]-thymidine into DNA. The relative specific radioactivity of DNA was decreased to 70% compared to controls. The norepinephrine level of the forebrain was reduced to 30-50% of the control value. The observed elevation of plasma corticosterone level did not appear to mediate the effect on cell proliferation. Kinetic studies indicated that the entry of precursor from the blood to the brain tissue was enhanced, but the higher tissue concentration of precursor was not utilized in the DNA synthesis with the same speed. The phosphorylation of radioactive thymidine to thymidine phosphates was only slightly inhibited, and the suppression of DNA synthesis was evident even after the correction made on the basis of concentration of radioactivity thymidine phosphates available for synthesis. DNA synthesis in the cerebellum was not suppressed by amphetamine treatment. The possible connection between the change in norepinephrine pools and the proliferative activity is considered.