Estradiol increases catecholamine levels in the hypothalamus of ovariectomized rats during the dark-phase

Estrogens modulate critical homeostatic functions of the hypothalamus such as temperature regulation, sexual behavior and sleep with the most pronounced effects in rats occurring during the dark-phase. The neurochemical signals underlying estrogenic regulation of these hypothalamic functions have not been clearly identified, possibly due to the fact that previous studies have not explored the effects of estrogen treatments on neuronal signaling during the dark-phase. In the present study, ovariectomized rats received estradiol benzoate (5 μg/rat for 7 days, s.c.) and norepinephrine and dopamine levels were measured in the preoptic area of the hypothalamus across the light/dark cycle using in vivo microdialysis. Estradiol benzoate treatment increased extracellular norepinephrine and dopamine levels relative to vehicle treatment during the dark-phase. Increases in norepinephrine and dopamine were first detected by 30 min and 5.5 h after lights-off, respectively. Subsequent increases in norepinephrine and dopamine were also noted throughout the 9.5- h collection period. The effect of estradiol benzoate on catecholamine release did not correlate with increases in either tyrosine hydroxylase (TH) protein expression or activity levels in the anterior hypothalamus, although a marked decrease in TH activity correlated with a rise in extracellular norepinephrine at the beginning of the dark-phase. We conclude that subchronic estradiol benzoate treatment increases extracellular catecholamine levels in the preoptic area of the hypothalamus during the dark-phase without a concomitant increase in neurotransmitter biosynthesis. The estradiol benzoate-induced increases in norepinephrine and dopamine levels in the preoptic area during the dark-phase may play an important role in modulating critical hypothalamic functions.