Effects of age on GABA turnover rates in specific hypothalamic areas in female rats

During aging in female rats the estrous cycle ceases and the animals develo p phases of constant estrous (CE) or constant diestrous (CD) prior to the i rreversible transition into anestrous. In young rats, gamma-aminobutyric ac id (GABA) is of pivotal importance for the release of GnRH. In the medial-p reoptic area (MPO) where the majority of the GnRH perikarya are located in the rat, GABA release decreases at the time of the preovulatory LH surge. T he suprachiasmatic nucleus (SCN) contains numerous GABA neurons. Neurochemi cal signals from this hypothalamic nucleus provide temporal information to GnRH neurons and thereby influence the preovulatory LH surge and the length of estrous cycles. To investigate aging-related changes of the activity of hypothalamic GABAergic neurons, we determined GABA turnover rates in vario us hypothalamic nuclei of CE and CD rats and compared them to those determi ned in young estrous (E) or diestrous rats (D1). In old female rats, GABA activity in the MPO was significantly decreased co mpared to E and D1 rats. A selective increase of GABA turnover rates was ob served in the SCN of CE animals. No age-related changes were observed in th e other examined brain areas. These data provide the first evidence for alt erations in GABAergic activity in specific hypothalamic areas that depend o n age and reproductive status. These may cause changes in ability to induce preovulatory LN surges and to maintain regular estrous cyclicity.