Differential effects of estrogen and androgen on locomotor activity induced in castrated male rats by amphetamine, a novel environment, or apomorphine.

Four experiments were conducted using male rats to determine whether testosterone (T), or its neural metabolites estradiol (E2) and 5 alpha-dihydrotestosterone (DHT), influence the expression of locomotor activity, which is thought to depend in part on the activation of mesolimbic dopaminergic neurons. Subcutaneous implantation of silastic capsules containing E2, but not T or DHT, caused a significant increase in the amount of activity displayed by castrated rats which had been habituated to infrared photobeam activity cages prior to receiving an i.p. injection of D-amphetamine sulfate (1.5 mg/kg). Administration of E2, but not T or DHT, also significantly increased the amount of activity which other groups of castrated rats displayed when they were first placed in the photobeam cages. Likewise, administration of E2 but not T or DHT, to castrated rats which had previously received bilateral injections of 6-hydroxydopamine into the nucleus accumbens septi, caused a significant increase in the activity displayed in response to an i.p. injection of apomorphine HCl (1.0 mg/kg). However, administration of estrogen or androgen to castrated rats which were neurologically intact had no effect on the amount of stereotyped behavior displayed in response to increasing doses (1.0, 2.0 and 4.0 mg/kg) of apomorphine. It is suggested that the selective, facilitatory effect of E2 on drug- and novelty-induced locomotor activity resulted from increased postsynaptic receptor activation at dopaminergic synapses in the nucleus accumbens septi.