Neonatal androgen manipulation differentially affects the development of monoamine systems in rat cerebral cortex, amygdala and hypothalamus.

Neural tissue during perinatal life is sufficiently plastic to respond to the presence of testicular androgens. Here we studied the effect of neonatal androgen manipulation (castration of male and androgenization of female rats) on monoamine neurotransmitter systems in the cerebral cortex and sexually dimorphic regions of brain (hypothalamus and amygdala). Norepinephrine (NE) and dopamine (DA) concentrations in cortex, amygdala and hypothalamus of rats were assayed by HPLC at days 25, 60, 120, 180, 240 and 300. Results show that NE levels in all groups of rats at day 25 were higher in the hypothalamus (5-9 ng/mg protein) compared to the amygdala (0.5-3 ng/mg protein) and the cortex (0.5-1 ng/mg protein). Levels of DA at day 25 in the hypothalamus and the amygdala were comparable (up to 3.5 ng/mg) but higher than in the cortex (1.25-1.75 ng/mg protein). NE and DA concentrations in sham-castrated male and androgen-treated females were higher at day 25 compared to castrated male and control females in both amygdala and hypothalamus; however, levels of NE and DA remained unchanged in the cortex. Pattern of NE concentrations started reversing with increase in age, i.e., NE levels in control females and castrated males increased almost 4-fold in amygdala and 2-fold in hypothalamus by day 300, but there was no significant change in the cortex. Compared to that, NE levels decreased in sham-castrated male (2-fold) and androgen-treated females (3-fold) in amygdala as well as in the hypothalamus (2-fold) in both these groups. A similar pattern of reversal of DA levels was found in both amygdala and hypothalamus, however, at day 300 DA levels were comparable in all the four groups. These studies suggest that androgen manipulation (castration or androgen administration) induces age-dependent short- and long-term effects on the development of noradrenergic and dopaminergic systems in the sexually dimorphic regions of brain, amygdala and hypothalamus, without a significant change in the cerebral cortex.