Distribution of Benzodiazepine Binding Sites in the Brain of the Male Japanese Quail and Its Correlation to a Hormonal Control: Quantitative Autoradiography Study

Abstract

Quantitative receptor autoradiography was used to study the neuroanatomical distribution and effects of gonadal hormones on [³H] flunitrazepam binding in the male Japanese quail brain. In gonadally intact quail brains, [³H] flunitrazepam displayed a heterogeneous distribution, with elevated levels in the posterior brain regions such as the stratum griseum et fibrosum superficiale and stratum griseum centrale of the optic tectum. Lower values were observed in the anteriorly located brain sites such as the nucleus septalis (lateralis et medialis), the cortex dorsolateralis and the nucleus lateralis hypothalami. Castration affected [³H] flunitrazepam binding levels in brain areas known to contain gonadal steroid receptors as well as in some areas which were devoid of gonadal steroid receptors. Castration in fact, elevated [³H] flunitrazepam binding in the nucleus preopticus anterior and reduced binding levels in archistriatum dorsalis et ventralis and in the nucleus intercollicularis; all of these areas are known to have gonadal steroid receptors. In two regions which do not contain such receptors, namely the hyperstriatum ventrale and the cerebellum pars granularis, castration increased [³H] flunitrazepam binding. In order to determine whether the gonadal steroid effect is due to changes either in the number of binding sites (B_max) and or affinity binding state (KD), saturation binding studies were carried out in some of the areas described above in brains of quail which were castrated or castrated and given replacement therapy with testosterone or estradiol for 2 weeks. In keeping with the suppressive effect of the gonads inferred from the castration results described above, testosterone and estradiol decreased the B_max of [³H] flunitrazepam binding in the hypothalamus preoptic area, while in hyperstriatum ventrale only estradiol produced a significant decrease of the B_max. We then tested for the effects of GAB A on [³H] flunitrazepam binding to the receptors and found that GABA intensified the depressive activity of gonadal steroid replacement therapy in the hyperstriatum ventrale and in the hypothalamus-preoptic area as shown respectively by the approximate 45 and 40% greater decrease of B_max. However when the GABA effect on [³H] flunitrazepam binding in the presence of GABA was expressed as ratio, only the hyperstriatum ventrale revealed a significantly enhanced potentiation effect following castration, while a significant suppression of this potentiation effect was obtained by both T and E replacement therapy. These results suggest that a GABA-benzodiazepine receptor interaction might be involved in the regulation of some hormone-mediated cerebral functions in the male quail such as neuroendocrine and sociosexual behavior.

Distributions of GABAA, GABAB, and benzodiazepine receptors in the forebrain and midbrain of pigeons

“…Our work in pigeon and work by others in quail shows that the dense GABA innervation in the avian visceral basal ganglia is only moderately well matched by the presence of GABAA/BDZ and GABAB receptors (Canonaco et al, 1991(Canonaco et al, , 1992Veenman and Reiner, 1994). The same is true for the GABA innervation and GABAA/BDZ and GABAB receptors in the mammalian visceral basal ganglia (Nagai et al, 1984;Mugnaini and Oertel, 1985;Schoch et al, 1985;Penney and Pan, 1986;Richards et al, 1987;Chu et al, 1990;Churchill et al, 1991;Zhanget al, 1991;Wisden et al, 1992).…”

Performance of appetitive or consummatory components of male sexual behavior is mediated by different brain areas: a 2-deoxyglucose autoradiographic study

“…If the metabolic changes observed in the nucleus intercollicularis of birds performing copulatory behavior relate to vocalization, one would then have to assume that the increased 2-DG incorporation reflects the activation of inhibitory circuits. In agreement with this interpretation it has been shown that the quail nucleus intercollicularis contains high densities of GABA receptors 32,33 that could represent the neurochemical substrate for this behavioral inhibition (see Ref. 66 for discussion).…”

Dimorphic distribution of the two main GABAA binding sites in cortical and limbic areas of a rodent living in natural environmental conditions

“…The further demonstration of elevated BDZ receptor levels, through the [ 3 H] MUS/[ 3 H] FLU ratios, being more or less equal to unity in the hypothalamus and in some telencephalic regions of the limbic system of both the male and female woodland mice (Table 3) seems to underlie an interesting phylogenetic relationship. Such a ratio has to date been reported only for laboratory rodents (Canonaco et al, 1989, whereas a higher [ 3 H] MUS/[ 3 H] FLU ratio has been reported for nonmammalian species (Canonaco et al, 1991(Canonaco et al, , 1992Tavolaro et al, 1993). The increased amount of the BDZ site, in line with the lower [ 3 H] MUS/[ 3 H] FLU ratios in mammalian limbic and cortical regions, places strong emphasis on the importance of the a subunit (specific for this GABA A supramolecular site) in cerebral GABAergic activities of mammals.…”

“…These archistriatum-derived areas are known to be involved in the regulation of social behaviors, including aggressive-defensive (Kemble et al, 1990) and lordotic (Chateau and Aron, 1989) (Pfaff and Keiner, 1973;Simerly et al, 1990), noted for lordotic behaviors in the female rodent (Masco and Carrer, 1980), seem to point to the GABA A site as the first and important component in the control of reproductive behaviors in this phylogenetically better conserved area. This relationship seems to be further strengthened by the high GABA A receptor content in the homologous brain area of amphibians (Tavolaro et al, 1993) and in the amygdaloid region of birds (Canonaco et al, 1992). It is only in a subsequent stage, with the establishment of more complex telencephalic regions in mammalian species (Butler, 1994), that the expression of higher behavioral functions seems to have been shifted to other GABA A supramolecular sites in some amygdala areas.…”

“…In the few works considered, contrasting effects induced by the BDZs in the brain of nonmammalian vertebrates (Witkin and Barrett, 1985) have been attributed to a species-specific factor. From these works, the biochemical and pharmacological differences of the GABA A molecule have proven to be important factors in the modification of anxiety-related behaviors in both anamniote (Schmitz et al, 1988;Corda et al, 1989;Tavolaro et al, 1993) and amniote (Canonaco et al, 1991(Canonaco et al, ,1992Veenman et al, 1994) vertebrates. There have also been behavioral studies that have shown that the aggregation patterns of rodent species within their territory (Wenzel, 1974), associated with the alteration of cerebral neuronal substrates, are key elements in the success of naturally occurring sociosexual activities (Fernandez-Guasti et al, 1990).…”