TIME-COURSE OF THE EFFECTS OF STEROID-HORMONE DEPRIVATION ELICITED BYOVARIECTOMY OR OVARIECTOMY PLUS ADRENALECTOMY ON THE AFFINITY AND DENSITY OF GABA BINDING-SITES IN DISTINCT RAT-BRAIN AREAS

The time course of the behaviour of GABA(A) receptors (affinity of mus cimol for GABA binding sites and their number) in membranes obtained f rom five distinct rat brain areas was evaluated in dependence of the d ecline of the serum concentrations of estradiol and progesterone follo wing hormone deprivation by either ovariectomy (OVX) or ovary- plus ad renalectomy (OVX-ADX) after 1, 2, 3, 5, 14 and 30 days. Diestrus rats served as control. The effect of OVX on the GABA binding sites was due to a decrease of affinity rather than alterations in their density. C onversely, the combined surgery of OVX plus ADX affected both the affi nity and the density. Also, the OVX-linked changes of muscimol binding were observed only after five days as compared to control animals, wh ile the initial OVX-ADX associated changes occurred already after one day. OVX-ADX produced significant decreases in the number of binding s ites at the shortest times investigated, in frontal cortex (FC) at day one and two and in the medulla oblongata (MED) after three days, whic h disappeared in the subsequent times studied. Concomitant with the ma jor decrease of steroid hormone serum levels one day after OVX-ADX the FC displayed an increase in affinity by 45%. From the time when stero id serum levels are low the alterations in affinity elicited by both O VX-ADX and OVX only take a similar course, reflected by the following decrease in affinity. In MED an additional adrenalectomy did not signi ficantly modify the OVX linked decrease of affinity, except that the i nitial effect was already evident two days after OVX-ADX. The cerebell um (CER) displayed an increase of affinity only following OVX-ADX afte r one and two days, while the affinity determined in the hippocampus ( HIP) and hypothalamus (HYP) was not affected by either OVX or OVX-ADX. These findings show that the brain areas investigated behave differen tly to peripheral steroid hormone deficit and argue strongly in favour of a dual steroid hormone action: The effect of OVX on the GABAA rece ptor complex may be primarily mediated by an indirect mechanism of ste roid action while the effect of an additional ADX seems to include dir ect steroid actions.