GABA(A) RECEPTOR-MEDIATED RESPONSES IN THE VENTROMEDIAL NUCLEUS OF THE HYPOTHALAMUS OF FEMALE AND MALE NEONATAL RATS

Perinatal exposure of the developing brain to gonadal steroids during a limited critical period induces permanent, organizational difference s in neural structures between male and female animals. These differen ces are believed to underlie the manifestation of sexually dimorphic b ehaviors. Gamma-aminobutyric acid type A (GABA(A)) receptors expressed in the ventromedial nucleus (VMN) of the hypothalamus appear to be a key component underlying the expression of sexually dimorphic behavior s in rats. Specifically, GABA(A) receptor levels are known to be stero id regulated and sexually dimorphic, and GABA(A)-mediated transmission within the VMN is critical for the expression of sexual behavior in f emale, but not male, rats. Here we report that analysis of VMN neurons from neonatal rats revealed significant sex-specific differences in G ABA(A) receptor channel properties. Specifically, GABA(A)-mediated cur rents elicited by direct agonist application decayed more rapidly in V MN neurons from females than from males. Kinetic differences became mo re pronounced during the first 2 weeks of postnatal development. Analy sis of small, spontaneous inhibitory postsynaptic currents recorded in intact slices indicated a trend towards slower responses in neurons f rom males than females, but the differences in decay kinetics were not significant. Sex-specific differences in GABA(A) receptor kinetics ma y arise from activation of receptors not receiving synaptic contacts i n the slice preparation or may become apparent at intact synapses unde r conditions of increased activity and evoked release.