Regional and selective effects of oestradiol and progesterone on NMDA and AMPA receptors in the rat brain

We investigated the effect of 10 months ovariectomy and a correction therap y, 2 weeks before the rats were killed, of oestradiol, progesterone or thei r combination on NMDA and AMPA receptor binding in the hippocampus, dentate gyrus, striatum, nucleus accumbens and frontal cortex of the rat brain as well as on amino acid levels in frontal cortex. NMDA and AMPA binding densi ties were assayed by autoradiography using, respectively, L-[H-3]glutamate and [H-3]AMPA; amino acid concentrations were measured by high performance liquid chromatograhy (HPLC) coupled with UV detection. Ovariectomy was with out effect on NMDA and AMPA binding density in all brain regions assayed ex cept in the hippocampal CA1 region and dentate gyrus where it decreased NMD A binding density compared to intact rats values. Oestradiol restored and i ncreased NMDA binding density in the CA1 subfield and the dentate gyrus of ovariectomized rats but, by contrast, it decreased binding density in the s triatum and in the frontal cortex while having no effect in the CA2/3 subfi eld of the hippocampus and in the nucleus accumbens. Oestradiol was without effect on AMPA binding density in the hippocampus and the dentate gyrus bu t it reduced AMPA binding density in the striatum, the frontal cortex and t he nucleus accumbens. Progesterone, and oestradiol combined with progestero ne, decreased NMDA but not AMPA binding density in the frontal cortex of ov ariectomized rats, and they were without effect on these receptors in the o ther brain regions assayed. Amino acid concentrations in the frontal cortex were unchanged after ovariectomy or steroid treatments. The effect of oest radiol in the hippocampus confirmed in the present study and our novel find ings in the frontal cortex, striatum and nucleus accumbens may have functio nal significance for schizophrenia and neurodegenerative diseases.