Type I corticosteroid receptors modulate PTZ-induced convulsions of withdrawal seizure prone mice

Roberts, Amanda J.; Crabbe, John C.; Keith, L

doi:10.1016/0006-8993(93)90573-6

Cited by 24 publications

(2 citation statements)

References 30 publications

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“…Finally, the excitatory versus inhibitory effects of CORT are mediated by mineralocorticoid (MR) and glucocorticoid (GR) receptors in the brain, with predominant MR activation increasing excitatory hippocampal output (discussed in De Kloet et al, 1998). Relevant to the present study, activation of MR exerted a proconvulsant effect against pentylenetetrazol-induced convulsions in WSP mice (Roberts et al, 1993), and acute EtOH withdrawal severity was significantly increased by acute and chronic administration of CORT in WSP mice (Roberts et al, 1991, 1994). However, even though the proconvulsant effect of exogenous administration of CORT is fairly well-established, it should be noted that deoxycorticosterone (DOC, precursor to CORT) has been reported to have anticonvulsant properties due to its 5α-reduction to GABAergic metabolites (Reddy and Rogawski, 2002).…”

Section: Discussionsupporting

confidence: 63%

Sex differences in acute ethanol withdrawal severity after adrenalectomy and gonadectomy in Withdrawal Seizure-Prone and Withdrawal Seizure-Resistant mice

Strong¹,

Kaufman²,

Crabbe

et al. 2009

Alcohol

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Recent findings suggest that the ability of ethanol (EtOH) to increase the levels of neurosteroids with potent γ-aminobutyric acid (GABA)ergic properties can influence measures of EtOH sensitivity. Earlier studies determined that removal of the adrenals and gonads diminished the steroidogenic effect of EtOH and significantly increased acute EtOH withdrawal severity in two inbred mouse strains that differed in withdrawal severity, suggesting the contribution of anticonvulsant GABAergic steroids to acute withdrawal in intact animals. Thus, the goal of the present studies was to investigate the consequence of steroid removal on acute EtOH withdrawal through excision of the adrenals and gonads, in another genetic animal model of EtOH withdrawal differences, the Withdrawal Seizure-Prone (WSP) and -Resistant (WSR) selected lines. Male and female WSP and WSR mice underwent surgical removal of the adrenals and gonads or no organ removal (SHAM). One to two weeks later, baseline handling-induced convulsions (HICs) were assessed, mice were given a 4 g/kg dose of ethanol, and HICs were measured hourly for 12 hours and then at 24 hours. The combination surgery significantly increased EtOH withdrawal in WSP and WSR female mice, as measured by area under the curve (AUC) and peak HIC scores. AUC was significantly positively correlated with plasma corticosterone levels and significantly negatively correlated with progesterone levels. In contrast, surgical status did not alter withdrawal severity in male WSP and WSR mice. Overall, the increase in acute ethanol withdrawal severity in female WSP and WSR mice following adrenalectomy and gonadectomy corroborate our recent evidence that withdrawal from a high dose of EtOH can be modulated by anticonvulsant steroids produced in the periphery.

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Section: Discussionsupporting

confidence: 63%

Sex differences in acute ethanol withdrawal severity after adrenalectomy and gonadectomy in Withdrawal Seizure-Prone and Withdrawal Seizure-Resistant mice

Strong¹,

Kaufman²,

Crabbe

et al. 2009

Alcohol

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“…A dose of 150 mg/kg was administered s.c. in a total volume of 0.1 ml. This dose has been shown to induce forelimb flexion reliably in 15‐day‐old rats (1,10).…”

Section: Methodsmentioning

confidence: 99%

The Acute Anticonvulsant Effects of Deoxycorticosterone in Developing Rats: Role of Metabolites and Mineralocorticoid‐receptor Responses

Edwards¹,

Vimal²,

Burnham³

2005

Epilepsia

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Summary:Purpose: The mechanisms that mediate the acute anticonvulsant effects of deoxycorticosterone (DOC) were investigated in young rats.Methods: Fifteen-day-old rats were pretreated with a variety of compounds, including (a) agonists of the receptors that bind DOC (mineralocorticoid receptors); (b) the DOC 5α− and 5α-3α-reduced metabolites, plus agonists that bind the receptors of the 5α−reduced metabolite of DOC (progesterone receptors); and (c) DOC itself in the presence and absence of metabolism and receptor blockers. Fifteen minutes later, pentylenetetrazol (PTZ) was administered, and maximal pentylenetetrazol (MMT) seizure responses were scored.Results: Agonists of mineralocorticoid receptors increased the latency to forelimb flexion in PTZ seizures and sometimes suppressed the seizures completely. At low, nonconvulsant doses, spironolactone (a mineralocorticoid-receptor antagonist) blocked the anticonvulsant effects of a nonsedating, but not a sedating, dose of DOC. These data suggest the possible direct involvement of mineralocorticoid receptors in the anticonvulsant effects of DOC. At low, nonconvulsant doses, finasteride (which blocks the metabolism of DOC) partially blocked the protective effects of DOC, suggesting the contribution of metabolites to the anticonvulsant actions of DOC. Dihydrodeoxycorticosterone (DHDOC)-the first metabolite of DOC, an agonist at progesterone receptors, and an allosteric modulator of the γ -aminobutyric acid (GABA) A receptor-and tetrahydrodeoxycorticosterone, a secondary metabolite of DOC and an allosteric modulator of the GABA A receptor, both blocked MMT seizures.Conclusions: These findings suggest that both DOC and its metabolites may contribute to the anticonvulsant effects seen in young rats, perhaps acting via interactions with several different receptors.

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Herbal Medicines and Epilepsy: The Potential for Benefit and Adverse Effects

Spinella

2001

Epilepsy & Behavior

119

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Type I corticosteroid receptors modulate PTZ-induced convulsions of withdrawal seizure prone mice

Cited by 24 publications

References 30 publications

Sex differences in acute ethanol withdrawal severity after adrenalectomy and gonadectomy in Withdrawal Seizure-Prone and Withdrawal Seizure-Resistant mice

Sex differences in acute ethanol withdrawal severity after adrenalectomy and gonadectomy in Withdrawal Seizure-Prone and Withdrawal Seizure-Resistant mice

The Acute Anticonvulsant Effects of Deoxycorticosterone in Developing Rats: Role of Metabolites and Mineralocorticoid‐receptor Responses

Herbal Medicines and Epilepsy: The Potential for Benefit and Adverse Effects

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