Regulation of gamma-aminobutyric acidB (GABAB) receptors in cerebral cortex during the estrous cycle.

We examined binding of the GABAB 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 found that the binding of baclofen to neocortical membranes varied systematically as a function of the estrous cycle, with the lowest binding occurring during the estrus stage. Binding to archicortical (hippocampal) and hypothalamic preparations also varied with the estrous cycle, except that the lowest level of binding in these latter cases occurred during the diestrus stage. The variation of [3H]baclofen binding during the estrous cycle was different with respect to the binding of [3H]muscimol, an agonist for GABAA receptors, and [3H]8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), an agonist for serotonin 5-HT1A receptors that shares similar G proteins and effectors with GABAB receptors. Saturation binding studies of cortical GABAB receptors showed that apparent receptor density (Bmax) rather than affinity (Kd) best accounted for the change in binding during the estrous cycle in that Bmax, like total specific binding, was at a minimum during the estrus stage. The robust regulation of GABAB receptors in neocortex was unexpected and its functional significance is at present unknown. However, the correlation of the menstrual cycle with mood and other behavioral changes, and the correlations of the estrous and menstrual cycles with seizure susceptibility, may somehow depend upon hormonal regulation of transmitter systems such as the one we have observed here.