An autoradiographic study comparing the interactions of 3 alpha-OH-5 alpha-pregnan-20-one, pregnenolone sulfate and pentobarbital with [3S]-TBPS binding sites and their modulation by GABA in different structures of the rat brain.

Using quantitative autoradiography, we have studied the distribution of the [35S]-TBPS binding sites of the GABA-A receptor complex in various structures of the rat brain. High densities of binding sites were observed in layer IV of the cerebral cortex, in the globus pallidus, and in the thalamus. Intermediate densities of binding sites were observed in superficial and deep layers of the cerebral cortex, in the dentate gyrus and in the hippocampus. For all of these structures, the interactions of 3 alpha-OH-5 alpha-pregnan-20-one (3 alpha 5 alpha P), pregnenolone sulfate (PS), and pentobarbital with [35S]-TBPS binding, in the presence or the absence of GABA were studied. In the absence of GABA, IC50 values for the inhibition of [35S]-TBPS binding were 10(-6) M for 3 alpha 5 alpha P and 10(-4) M for PS and pentobarbital in all of the brain regions studied. In the presence of GABA (5 x 10(-6) M), IC50 values were decreased by one order of magnitude for 3 alpha 5 alpha P, PS, and pentobarbital in all structures studied except layer IV of the cortex, where the IC50 value for PS was more markedly decreased (up to two orders of magnitude). By contrast, IC50 values for picrotoxin and TBPS to inhibit [35S]-TBPS binding were 10(-7) M and 10(-8) M, respectively, in the presence or absence of GABA.