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In an effort to establish distinct phylogenetic values for the major GABA(A) receptor subunit mRNAs (alpha(1), beta(2) and gamma(2)) in the telencephalon, the cellular expression capacity of these mRNAs was evaluated in this brain region of two distantly related mammals (hedgehog and rat). Application of emulsion hybridization histochemistry and quantitative film autoradiography approaches allowed us to detect elevated ( P0.01) beta(2) mRNA levels in primitive telencephalic neuronal populations such as those of the glomerular olfactory layer of the hedgehog. Conversely, notable levels of the alpha(1)-subunit mRNA were also registered for the higher telencephalic regions such as the oriens-pyramidalis layer of the hippocampus although elevated levels were mostly obtained for the rat. Interestingly, it was the high number of giant pyramidal neurons that were actively involved in the expression of this subunit. A similar pattern was also detected for pyramidal-like cells of the rat lateral amygdala region expressing the gamma(2)-subunit mRNA. Taken together, these results suggest an early phylogenetic success of GABAergic neuronal mechanisms relying mainly on elevated beta(2)-subunit levels. On the other hand, elevated quantities of gamma(2)- and, above all, of alpha(1)-subunit mRNAs in the rat seem instead to be related to the highly advanced behavioral and mnemonic strategies that are under the control of these telencephalic regions.

This investigation represents a first study dealing with the dimorphic differences of the main alpha-containing gamma-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 alpha1-enriched and of alpha2/3-enriched and alpha5-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 (P0.001) GABA-dependent reduction of zolpidem inhibition constants was mostly registered in alpha1- and/or alpha5-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 alpha1- with alpha2/3-subunits or by all three alpha-subunits. These results support the contention that a sex-related alpha-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.

Quantitative autoradiography was used to investigate the distribution and effects of gonadal hormones on [3H] muscimol (specific GABAA receptor ligand) binding in the male Japanese quail brain. In gonadally intact Japanese quail brains, [3H] muscimol revealed a heterogeneous distribution with high GABAA receptor levels in the cerebellum pars granularis (656 fmol/mg wet weight of tissue) and in the pars molecularis (405 fmol/mg wet weight of tissue). Low receptor levels were found in the nucleus preopticus anterior and the nucleus lateralis of the hypothalamic regions (

Quantitative receptor autoradiography was applied to evaluate the effects of one and three injections of 1 mg progesterone (P) on 3H muscimol binding levels in the different forebrain areas of the female hamster. The overall effect of P resulted in substantial increases in 3H muscimol binding in brain areas containing gonadal steroid receptors: medial preoptic area and ventromedial hypothalamic nucleus as well as in bed nucleus stria terminalis and subiculum. Similarly, the caudate putamen, a region where gonadal steroid receptors are not abundant, also showed substantial increases of 3H muscimol binding receptor levels. Moreover, female hamsters treated with P for 3 days presented altered 3H muscimol binding levels in the amygdala and thalamic nucleus that were, in some cases, not produced by one dose of P. P treatment also decreased GABAA binding in two areas of the thalamus. These results are consistent with the proposal that P may alter GABAergic inhibitory activity via changes in the levels of GABAA receptors in certain forebrain areas in the female hamster, changes which may be linked to the mediation of anxiolytic effects and to the inhibition of aggressive behavior. These data also suggest that P treatment increases the binding of high affinity GABA receptors in some forebrain sites and may be responsible for maintenance of the anxiolytic effects.

The levels of gamma amino butyric acid (GABAA) receptors (i.e. 3H-Muscimol binding sites) were determined by quantitative neurotransmitter receptors autoradiography in ovariectomized (OVX), OVX-estradiolo (E), OVX-progesterone (P), OVX-E + P, diazepam (DZ) and DZ + Ro15-1788 treated female hamsters. The various hormonal treatments altered 3H muscimol binding in many brain areas, whereas DZ and DZ + Ro15-1788 had little influence on GABAA receptor levels at the onset of the blocked aggressive behavioral activity. For example, E, P and E + P all significantly increased 3H muscimol binding in medial preoptic area, ventromedial hypothalamic nuclei, and vertical diagonal bandmedial septal nucleus, whereas P treatment increased binding in the caudate-putamen and decreased it in reuniens nucleus of the thalamus. E and E + P treatments increased 3H muscimol binding in the corticomedial amygdala nucleus and hippocampus. Diazepam treatment decreased the GABAA receptor binding in the caudate-putamen and basolateral amygdala, while having no effect in the other brain regions where hormone treatment was effective. In vitro incubation of brain sections with micromolar concentrations of E or P did not change muscimol binding. These results suggest that ovarian steroids, and benzodiazepines to a lesser extent, modulate 3H muscimol binding but do so in different brain regions. The hormone effects on 3H muscimol binding in the critical reproductive centres at a time period that coincides with the onset of its behavioral effect is consistent with a genomic controlled activity.