Differential modulation of [3H]flunitrazepam binding in female rat brain by sex steroid hormones

Canonaco, Marcello; Valenti, Antonella; Tavolaro, Renata; Bettini, Ezio; Maggi, Adriana

doi:10.1016/0014-2999(89)90140-4

Cited by 16 publications

(16 citation statements)

References 11 publications

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“…In addition, gona dal hormone effects were not limited to steroid-concen trating areas as revealed by effects of castration in brain areas which are also known to be devoid of steroid recep tors [30], namely the Cb gr and HV. At present, the only hormone-mediated regulation of BZ receptor levels has been shown in the different regions of the rodent brain and also in this case, the hormonal effect was mainly lo calized in areas that contain sex steroid receptors [7]. Fur thermore, a steroid-dependent activity responsible for the altered GABA receptor function has been shown, in the cerebellum (cerebral structure lacking cytosolic steroid re ceptors) of the rat brain [27].…”

Section: Discussionmentioning

confidence: 99%

“…The hormone effects on BZ re ceptor changes may very probably be mediated through a GABAdependent modulatory activity, as already revealed in rat brain [7,18]. Since this substance is removed during the preincubation washes, a final GABA (Sigma) concentration of 50 pA/, used in the rat brain slices [7], was included in another parallel incubation. A third incubation, containing a final diazepam concentration of 10 pA/, was included to correct for nonspecific binding.…”

Section: Binding Studymentioning

confidence: 99%

“…In addition, since an allosteric coupling of BZ and GABA receptors to a chloride ionophore as well as the ability of GABA to increase BZ binding has been exten sively shown in mammalian brain areas [7,18], we also looked for possible changes in GABA-induced modula tions of these sites in the quail brain. The addition of GABA to the incubation evoked a greater depressive ef-Bound,fmol/mg protein feet of the gonadal steroid therapy on the binding of [3H] FLU to the receptors.…”

Section: Binding Studymentioning

confidence: 99%

“…BZ receptors were labeled in vitro with the specific ligand [3H] flunitrazepam (FLU) using the method applied for rodent brain [7] plus some modificatons. Briefly, brain sections were thawed and preincubated for 3 x 10 min in 50 mM ice-cold Tris-HCI buffer (pH 7.4) to remove as much endogenous material as possible.…”

Section: Quantitative Receptor Autoradiographymentioning

confidence: 99%

“…Currently, endocrine studies have also demon strated that BZ is involved in the hormonal secretion from both pituitary [12,15] and peripheral endocrine tissues [3], The above results have aroused interests towards the characterization of BZ receptors in rodent CNS [28,29] and hence it is not surprising that most biochemical and distribution data of the BZ receptors are basically con fined to mammalian species. In fact, recent studies have revealed a hormone-dependent regulation of BZ recep tors in the different brain areas of the rat [7,10],…”

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confidence: 99%

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

Canonaco

Tavolaro²,

Cerra³

et al. 1992

Neuroendocrinology

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Binding Studymentioning

confidence: 99%

Section: Binding Studymentioning

confidence: 99%

Section: Quantitative Receptor Autoradiographymentioning

confidence: 99%

mentioning

confidence: 99%

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

Canonaco

Tavolaro²,

Cerra³

et al. 1992

Neuroendocrinology

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Anxiolytic Effects of Steroid Hormones during the Estrous Cycle

Brot

Koob

Britton

2002

Recent Developments in Alcoholism

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The modulation of brain dopamine and GABAA receptors by estradiol: A clue for CNS changes occurring at menopause

Bossé

Paolo

1996

Cell Mol Neurobiol

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1. Tardive dyskinesia is more important in postmenopausal women than men of comparable age and a peak of first episodes of schizophrenia is observed in postmenopausal women. The effect of ovariectomy (2 weeks or 3 months) in rats was investigated as a model of decreased gonadal function associated with menopause. 2. Frontal cortex D1 receptor density and affinity were similar in intact male compared to intact female rats and progressively decreased in density with time after ovariectomy, with no change of affinity. Striatal D1 and D2 receptors also decreased in density after ovariectomy for both receptor subtypes, with no change of affinity. Striatal D1 receptor density and affinity were similar in intact male and female rats, whereas the density of D2 receptors was higher in females. Treatment with estradiol for 2 weeks restored the D2 but not the D1 receptor changes. 3. In the substantia nigra pars reticulata, striatum, nucleus accumbens, and entopeduncular nucleus, a progressive increase in [3H]flunitrazepam specific binding associated with GABAA receptors was observed as a function of time following ovariectomy; this was corrected with estradiol treatment. In contrast, the opposite was observed for [3H] flunitrazepam binding in the globus pallidus, where ovariectomy decreased binding, which was corrected with estradiol replacement therapy. 4. Low prefrontal cortex dopamine activity with implications of D1 receptors in negative symptoms of schizophrenia is hypothesized. Furthermore, GABAergic overactivity in the internal globus pallidus-substantia nigra pars reticulata complex is hypothesized in tardive dyskinesia. 5. The present data suggest that gonadal hormone withdrawal by reducing brain dopamine receptors and producing an imbalance of GABAA receptors in the output pathways of the striatum may predispose to schizophrenia and dyskinesia.

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Differential modulation of [3H]flunitrazepam binding in female rat brain by sex steroid hormones

Cited by 16 publications

References 11 publications

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

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

Anxiolytic Effects of Steroid Hormones during the Estrous Cycle

The modulation of brain dopamine and GABAA receptors by estradiol: A clue for CNS changes occurring at menopause

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