INFLUENCE OF GENDER AND BRAIN REGION ON NEUROSTEROID MODULATION OF GABA RESPONSES IN RATS

Neuroactive steroid derivatives of progesterone, testosterone and gluc ocorticoids can alter physiological responses to gamma-aminobutyric ac id (GABA), apparently through direct, non-steroid receptor mechanisms. The present study examined gender-related differences and regional va riations in the ability of tetrahydrodeoxycorticosterone (THDOC), 3 al pha-hydroxy-5 alpha-pregnan-20-one (3 alpha-5 alpha-THP, tetrahydropro gesterone), androsterone, and dihydroandrosterone (DHA) to alter physi ological GABA responses. Steroid modulation of GABA-activated (36)chlo ride influx into microsac preparations from cortex, hippocampus, amygd ala, cerebellum and hypothalamus-preoptic area in adrenalectomized-gon adectomized rats of both sexes were tested. The effects of THDOC and 3 alpha-5 alpha-THP were also examined in groups of intact male and fem ale rats. All four steroids increased GABA-activated chloride influx, although the maximal enhancement in GABA responses differed significan tly among brain regions. The rank order of maximal THDOC and 3 alpha-5 alpha-THP effects was hippocampus > cortex similar to amygdala > hypo thalamus-preoptic area similar to cerebellum. Regional differences in potentiation of GABA responses were seen with androsterone, but not di hydroandrosterone. The rank order of androgenic potentiation of GABA r esponses was amygdala similar to hippocampus > cortex similar to HPA > cerebellum. Slight gender-related differences in responses to steroid s were seen with THDOC, with males showing greater maximal enhancement of GABA responses with THDOC than females in the amygdala and hypotha lamus-preoptic area. Since sex differences were observed with the gluc ocorticoid derivative THDOC, but not the progesterone derivative 3 alp ha-5 alpha-THP or androgenic steroids, it appears neuroactive steroid modulation of GABA responses can be differentially affected by the hor monal milieu in a regionally-specific manner.