Developmental sex differences in amino acid neurotransmitter levels in hypothalamic and limbic areas of rat brain

GABA, glutamate and aspartate are the predominant amino acid neurotransmitt ers in the mammalian brain. We have previously reported a developmental sex difference in messenger RNA levels of glutamate decarboxylase, the rate-li miting enzyme in GABA synthesis [Davis A. M. et al. (1996) Horm. Behav. 30, 538-552]. Males were found to have significantly higher levels of messenge r RNA in many steroid-concentrating regions of the hypothalamus and limbic system on day 1 of life. Therefore, in this study, we have examined levels of amino acid neurotransmitters during early postnatal development in many of the same or related brain areas. We found that levels of all three trans mitters change as animals age. While both GABA and aspartate concentrations increase, glutamate levels decrease. In addition, there are sex difference s in neurotransmitter levels in several areas examined, including the ventr omedial and arcuate nuclei of the hypothalamus, and the CA1 region of the h ippocampus. Sex differences for GABA occur only on postnatal days 1 and 5. However, sex differences in aspartate occur later in development (postnatal day 20). The CA1 region of males has a significantly greater concentration of GABA, glutamate and aspartate than females on postnatal day 1. In addit ion, treatment of fi:males with testosterone propionate on the day of birth results in increased GABA levels, suggesting that these sex differences ma y be the result of hormone exposure during development. We hypothesize that these hormonally mediated sex differences in amino acid transmitters early in development contribute to the establishment of sexua lly dimorphic neuronal architecture in the adult. (C) 1999 IBRO. Published by Elsevier Science Ltd.