Mechanisms by Which Picrotoxin and a High Dose of Diazepam Elevate Plasma Corticosterone Level

Lakić, Nela; Peričić, Danka; Manev, Hari

doi:10.1159/000124547

Cited by 19 publications

(11 citation statements)

References 15 publications

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“…The blockade was achieved with a dose (0.5 mg/kg) which failed to affect plasma ACTH and corticosterone levels. Other in vivo studies show that picrotoxin (in doses of 1 mg/kg and higher) increases corticosterone secretion (Makara and Stark, 1974;Ixart et al, 1983;Peri~i6 et al, 1985;Laki6 et al, 1986). Our dose-response for picrotoxin confirmed the previous results.…”

Section: Discussionsupporting

confidence: 90%

“…With aim to elucidate the mechanism by which the lower dose of diazepam suppresses the HPA axis activity, we tried to counteract these inhibitory effects of diazepam on plasma ACTH and corticosterone levels in female rats with the antagonists of central (flumazenil; Hunkeler etal., 1981), and peripheral (PKl1195 or 1-(2-chlorophenyl)-Nmethyl-(1-methylpropyl-3-isoquinolinecarboxamide; Le Fur etal., 1983) benzodiazepine receptors and the antagonists of GABA (bicuculline) and GABA-A receptor coupled chloride channels (picrotoxin) (Olsen, 1982). As we have already shown in details the dose response effects and the time course of diazepam on plasma corticosterone levels (Peri6i6 et al, 1984) together with the mechanism of action of higher dose of diazepam on the HPA axis (Laki6 et al, 1986), in this paper we focused our attention on the effect of a lower dose of diazepam on the HPA axis.…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, in male rats diazepam (1 mg/kg) produced no change of plasma corticosterone levels (Peri6i6 etal., 1985). We presumed that the mechanism by which the higher dose of diazepam enhances plasma corticosterone levels does not involve the stimulation of GABA-A receptors, but rather the blockade of alpha-2 adrenergic receptors (Laki6 et al, 1986). With aim to elucidate the mechanism by which the lower dose of diazepam suppresses the HPA axis activity, we tried to counteract these inhibitory effects of diazepam on plasma ACTH and corticosterone levels in female rats with the antagonists of central (flumazenil; Hunkeler etal., 1981), and peripheral (PKl1195 or 1-(2-chlorophenyl)-Nmethyl-(1-methylpropyl-3-isoquinolinecarboxamide; Le Fur etal., 1983) benzodiazepine receptors and the antagonists of GABA (bicuculline) and GABA-A receptor coupled chloride channels (picrotoxin) (Olsen, 1982).…”

Section: Introductionmentioning

confidence: 99%

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Inhibitory effect of diazepam on the activity of the hypothalamic-pituitary-adrenal axis in female rats

Pivac

Peričić

1993

J. Neural Transmission

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The acute intraperitoneal administration of anxiolytic diazepam (2 mg/kg) inhibits the activity of the hypothalamic-pituitary-adrenal (HPA) axis, i.e., it decreases the concentration of adrenocorticotropic hormone (ACTH) and corticosterone in female rats. This fall of ACTH and corticosterone levels was reversed by an antagonist of central benzodiazepine receptors-flumazenil. The antagonist of peripheral benzodiazepine receptors-PK 11195, failed to affect diazepam-induced decrement of plasma ACTH and corticosterone levels. The suppressed HPA function obtained after diazepam administration was also antagonized by bicuculline, an antagonist of GABA recognition sites, and by picrotoxin, a drug that blocks the GABA-A receptor associated chloride channel. These results suggest that central benzodiazepine receptors, the part of GABA-A macromolecular complex, are involved in diazepam-induced inhibition of the activity of the HPA axis.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhibitory effect of diazepam on the activity of the hypothalamic-pituitary-adrenal axis in female rats

Pivac

Peričić

1993

J. Neural Transmission

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“…A va riety of clonidine responses has been shown to be mediated through postsynaptic «2-adrenergic receptors including re duction in cardiovascular function [27] and antagonism of elevated plasma corticosterone produced by various treat ments [16,29,53,54,62]. In support of this hypothesis that clonidine acts postsynapticaily at the level of the hypotha lamus to reduce CRF secretion, recent studies have shown ct2-adrenergic receptors to be localized on CRF-containing neurons in the paraventricular nucleus (PVN) [10].…”

Section: Discussionmentioning

confidence: 99%

Central Mechanisms of Ethanol-Induced Adrenocortical Response in Selectively Bred Lines of Mice

Jm¹,

Vg²

1987

Neuroendocrinology

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Selectively bred long-sleep (LS) and short-sleep (SS) mice differ markedly in ethanol-induced adrenocortical response. Intracerebroventricular injections of saline elicited a ‘stress-induced’ adrenocortical response in both lines of mice, and intracerebroventricular infusions of noradrenergic and cholinergic compounds modulated ethanol-induced and stress-induced adrenocortical responses differentially in these mice. Clonidine, an α₂-adrenergic agonist, blocked ethanol-induced elevations in plasma corticosterone in a dose-dependent manner (1 and 10 µg) in LS mice; however, only the 10-µg dose of clonidine effectively antagonized this response in SS mice. Clonidine was less effective in blocking adrenocortical activity induced by stress than that induced by ethanol. Yohimbine, an α₂-adrenergic antagonist, induced a marked elevation in plasma corticosterone in LS mice but not in SS mice; however, this compound did not alter ethanol-induced adrenocortical responses in either line of mice. Yohimbine reversed the inhibitory effect of clonidine in ethanol-treated LS and SS mice. Phentolamine, a nonspecific α-adrenergic antagonist, and propranolol, a β-adrenergic antagonist at high doses (10 µg), produced slight increases in plasma corticosterone in LS mice only. Neither these compounds nor methoxamine, a nonspecific α-adrenergic agonist, altered the effect of ethanol on adrenocortical activity in LS or SS mice. Carbachol, a mixed muscarinic/nicotinic agonist, significantly increased adrenocortical response in both LS and SS mice and potentiated ethanol-induced elevation in plasma corticosterone in both lines of mice. However, atropine, a nonspecific muscarinic antagonist, or hexamethonium, a nicotinic antagonist, did not modify ethanol-induced elevations in plasma corticosterone in LS and SS mice. These results suggest that adrenocortical activation produced by ethanol may be mediated primarily through central noradrenergic systems and that differences in these systems may account for the differential ethanol-induced elevation in plasma corticosterone exhibited by LS and SS mice.

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“…In rodents, this neu rotransmitter is mainly noted for its anticonvulsive and anxiolytic [21] as well as antiaggressive [6,26] behavioral effect. 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],…”

mentioning

confidence: 99%

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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Mechanisms by Which Picrotoxin and a High Dose of Diazepam Elevate Plasma Corticosterone Level

Cited by 19 publications

References 15 publications

Inhibitory effect of diazepam on the activity of the hypothalamic-pituitary-adrenal axis in female rats

Inhibitory effect of diazepam on the activity of the hypothalamic-pituitary-adrenal axis in female rats

Central Mechanisms of Ethanol-Induced Adrenocortical Response in Selectively Bred Lines of Mice

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

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