Time-dependent modulation by estrogen of amphetamine-induced hyperactivity in male rats

The effect of estradiol benzoate on the increase in activity induced by d-amphetamine (0.25 mg/kg) was studied in male rats. Both short latency and long latency effects were observed. Amphetamine-induced hyperactivity was increased 45 minutes after estradiol (50 micrograms/kg) administration, decreased one day later and again increased during the period 8-16 days after injection. At doses of 12.5 and 25 micrograms/kg, effects were smaller and not statistically significant, although they had a similar temporal pattern to the 50 micrograms/kg dose. The short-latency, presumably non-genomic, effect of EB was studied in more detail at 15, 30, 45 and 60 minutes after the administration of 50 micrograms/kg EB. An enhancement of the amphetamine-induced increase in locomotor activity reached its maximum 30 minutes after injection. The time factor was critical for the effects observed, and the results supported the view that estrogen may alter behavior mediated by dopaminergic pathways.