Dimorphic features of the different α-containing GABA-A receptor subtypes in the cortico-basal ganglia system of two distantly related mammals (hedgehog and rat)

Abstract.

This investigation represents a first study dealing with the dimorphic differences of the main α-containing γ-aminobutyric acid (GABA_A) receptors in the brain of two distantly related mammals (hedgehog and rat). The labeling of these receptors in the presence of zolpidem (highly selective benzodiazepine agonist) and under the different degree of GABA_A/benzodiazepine allosteric coupling activities accounted for a heterogeneous colocalization of α₁-enriched and of α_2/3-enriched and α₅-enriched GABA_A receptors in some areas of the cortico-basal ganglia system (including the important ventrolateral thalamic station) of both mammalian sexes. In the hedgehog, the greatest (P<0.001) GABA-dependent reduction of zolpidem inhibition constants was mostly registered in α₁- and/or α₅-enriched areas, such as the frontoparietal cortex lamina III (235%), ventrolateral thalamic nucleus (128%), and substantia nigra pars reticulata (110%) of the male. However, the greatest reductions in the rat were instead detected in the male substantia nigra pars reticulata (192%) and female striatum (120%), areas which are enriched either by the colocalization of α₁- with α_2/3-subunits or by all three α-subunits. These results support the contention that a sex-related α-containing GABA_A receptor sensitivity constitutes an important element in the execution of skilled motor activities during the different socio-sexual behaviors of the two mammals.