PROGESTERONE REGULATES GAMMA-AMINOBUTYRIC-ACID-B (GABA(B)) RECEPTORS IN THE NEOCORTEX OF FEMALE RATS

After discovering that binding to GABA(B) receptors in rat neocortex v aried as a function of the estrous cycle of the rat, we asked whether either or both of the major ovarian steroids could affect binding to G ABA(B) receptors in the same way, namely, by regulating the apparent d ensity (B-max) of GABA(B) receptors. We report here that in ovariectom ized rats, subcutaneous injection of progesterone alone, without the n ecessity of estrogen priming, increased the B-max of baclofen binding to GABA(B) receptors in the neocortex. Radioimmunoassay of plasma prog esterone before and after progesterone injections revealed that plasma progesterone levels similar to those reached during the progesterone surge in proestrus were associated with increased baclofen binding. Th e effect of progesterone upon baclofen binding was evident 4 h but not 1 h following progesterone treatment. There was some specificity with respect to the cortical receptors affected by progesterone in that un der our conditions, progesterone did not increase agonist binding to 5 -HT1A or GABA(A) receptors. We interpret our results to indicate that progesterone variation during the estrous cycle could be responsible f or a component of the regulation of GABA(B) receptors that occurs in n eocortex during the estrous cycle of the rat.