The Journal of Neurophysiology Vol. 81 No. 1 January 1999, pp. 192-203
Copyright ©1999 The American Physiological Society

Properties and Sex-Specific Differences of GABA_A Receptors in Neurons Expressing 1 Subunit mRNA in the Preoptic Area of the Rat

Sholeen T. Nett¹, Juan Carlos Jorge-Rivera¹, Margaret Myers¹, Ann S. Clark³, and Leslie P. Henderson^{1, 2}

¹ Department of Physiology and ² Department of Biochemistry, Dartmouth Medical School; and ³ Department of Psychology, Dartmouth College, Hanover, New Hampshire 03755 

Nett, Sholeen T., Juan C. Jorge-Rivera, Margaret Myers, Ann S. Clark, and Leslie P. Henderson. Properties and sex-specific differences of GABA_A receptors in neurons expressing 1 subunit mRNA in the preoptic area of the rat. J. Neurophysiol. 81: 192-203, 1999. Gamma-aminobutyric acid type A (GABA_A) receptors expressed within the medial preoptic area (mPOA) are known to play a critical role in regulating sexual and neuroendocrine functions. In the rat brain, high levels of expression of the 1 subunit mRNA of the GABA_A receptor are restricted to a limited number of regions that mediate sexual behaviors, including the mPOA. The biophysical and pharmacological profiles of native 1-containing receptors in neurons are unknown. Here, we have characterized the properties of GABA_A receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) and currents elicited by fast perfusion of GABA to isolated mPOA neurons of juvenile male and female rats. No significant sex-specific differences were evident in the mean peak amplitude, distribution of event amplitudes, kinetics of current decay, or the frequency of sIPSCs. The profile of modulation of sIPSCs by diazepam, -CCM and zolpidem, allosteric modulators that act at the benzodiazepine (BZ) site of the GABA_A receptor, support the assertion that mPOA neurons of both sexes express functional 1-containing receptors. The ability of zolpidem to modulate both sIPSC amplitude and currents elicited by rapid perfusion of GABA to mPOA neurons differed significantly between the sexes. Zolpidem reversibly induced negative 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 ~50% of control peak current amplitude. In situ hybridization analysis demonstrated that levels of the 1 subunit mRNA are significantly higher in mPOA neurons from male than female rats. No significant sex-specific differences were detected in the levels of 1, 2, or 5 mRNAs. These results suggest that native 1-containing receptors are expressed in primary neurons of the mPOA 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.

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