REGULATION OF GAMMA-AMINOBUTYRIC ACID(B) (GABA(B)) RECEPTORS IN CEREBRAL-CORTEX DURING THE ESTROUS-CYCLE

We examined binding of the GABA(B) receptor agonist baclofen to brain synaptic membranes as a function of the natural variations in gonadal steroids that occur during the estrous cycle of the adult rat. We foun d that the binding of baclofen to neocortical membranes varied systema tically as a function of the estrous cycle, with the lowest binding oc curring during the estrus stage. Binding to archicortical (hippocampal ) and hypothalamic preparations also varied with the estrous cycle, ex cept that the lowest level of binding in these latter cases occurred d uring the diestrus stage. The variation of [H-3]baclofen binding durin g the estrous cycle was different with respect to the binding of [H-3] muscimol, an agonist for GABA(A) receptors, and [H-3]8-hydroxy-2-(di-n -propylamino)tetralin (8-OH-DPAT), an agonist for serotonin 5-HT1A rec eptors that shares similar G proteins and effectors with GABA(B) recep tors. Saturation binding studies of cortical GABA(B) receptors showed that apparent receptor density (B(max)) rather than affinity (K(d)) be st accounted for the change in binding during the estrous cycle in tha t B(max), like total specific binding, was at a minimum during the est rus stage. The robust regulation of GABA(B) receptors in neocortex was unexpected and its functional significance is at present unknown. How ever, the correlation of the menstrual cycle with mood and other behav ioral changes, and the correlations of the estrous and menstrual cycle s with seizure susceptibility, may somehow depend upon hormonal regula tion of transmitter systems such as the one we have observed here.