Properties and sex-specific differences of GABA(A) receptors in neurons expressing gamma 1 subunit mRNA in the preoptic area of the rat

Gamma-aminobutyric acid type A (GABA(A)) receptors expressed within the med ial preoptic area (mPOA) are known to play a critical role in regulating se xual and neuroendocrine functions. In the rat brain, high levels of express ion of the gamma 1 subunit mRNA of the GABA(A) receptor are restricted to a limited number of regions that mediate sexual behaviors, including the mPO A. The biophysical and pharmacological profiles of native gamma 1-containin g receptors in neurons are unknown. Here, we have characterized the propert ies of GABA(A) receptor-mediated spontaneous inhibitory postsynaptic curren ts (sIPSCs) and currents elicited by fast perfusion of GABA to isolated mPO A neurons of juvenile male and female rats. No significant sex-specific dif ferences were evident in the mean peak amplitude, distribution of event amp litudes, kinetics of current decay, or the frequency of sIPSCs. The profile of modulation of sIPSCs by diazepam, beta-CCM and zolpidem, allosteric mod ulators that act at the benzodiazepine (BZ) site of the GABA(A) receptor, s upport the assertion that mPOA neurons of both sexes express functional gam ma 1-containing receptors. The ability of zolpidem to modulate both sIPSC a mplitude and currents elicited by rapid perfusion of GABA to mPOA neurons d iffered significantly between the sexes. Zolpidem reversibly induced negati ve modulation of currents in mPOA neurons isolated from male rats, but had no effect in mPOA neurons from female rats. Concentration-response analysis of responses in neurons acutely isolated from male rats indicated an IC50 of 58 nM with maximal decreases of similar to 50% of control peak current a mplitude. In situ hybridization analysis demonstrated that levels of the ga mma 1 subunit mRNA are significantly higher in mPOA neurons from male than female rats. No significant sex-specific differences were detected in the l evels of alpha 1, alpha 2, or alpha 5 mRNAs. These results suggest that nat ive gamma 1-containing receptors are expressed in primary neurons of the mP OA and that sex-specific differences in the expression of this subunit may contribute to sexual dimorphism in GABA(A) receptor modulation by compounds acting at the BZ site.