Neurosteroid Withdrawal Model of Perimenstrual Catamenial Epilepsy

Reddy, Doodipala Samba; Kim, Hee Yong; Rogawski, Michael A.

doi:10.1046/j.1528-1157.2001.10100.x

Cited by 145 publications

(135 citation statements)

References 50 publications

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“…In the etiology category, evidence has mounted that plummeting levels of progesterone (and progesterone-derived neuroactive steroids) may participate in catamenial epilepsy, a seizure disorder linked to the menstrual cycle (Reddy, 2004;Reddy et al, 2001;Rogawski, 2003;Rosciszewska et al, 1986). Neuroactive steroids have also recently been suggested to participate in dictating the latent period length in status epilepticus models of epileptogenesis (Biagini et al, 2006).…”

Section: B Other Neuropsychiatric Effects Involving Gaba a Receptorsmentioning

confidence: 99%

Mechanisms of neurosteroid interactions with GABAA receptors

Akk¹,

Covey²,

Evers³

et al. 2007

Pharmacology & Therapeutics

147

166

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Neuroactive steroids have some of their most potent actions by augmenting the function of GABA A receptors. Endogenous steroid actions on GABA A receptors may underlie important effects on mood and behavior. Exogenous neuroactive steroids have potential as anesthetics, anticonvulsants, and neuroprotectants. We have taken multiple approaches to understand more completely the interaction of neuroactive steroids with GABA A receptors. We have developed many novel steroid analogues in this effort. Recent work has resulted in synthesis of new enantiomer analogue pairs, novel ligands that probe various properties of the steroid pharmacophore, fluorescent neuroactive steroid analogues, and photoaffinity labels. Using these tools, combined with receptor binding and electrophysiological assays, we have begun to untangle the complexity of steroid actions at this important class of ligand-gated ion channel.

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Section: B Other Neuropsychiatric Effects Involving Gaba a Receptorsmentioning

confidence: 99%

Mechanisms of neurosteroid interactions with GABAA receptors

Akk¹,

Covey²,

Evers³

et al. 2007

Pharmacology & Therapeutics

147

166

View full text Add to dashboard Cite

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“…The maximal doses of FIN and DUT used in this study (80 and 100 mg/kg, intraperitonially, i.p., respectively) were selected based on preliminary investigations from our group and on evidence showing their ability to produce a full inhibition of 5AR in rodents after acute treatment (Kokate et al, 1999;Reddy et al, 2001;Reddy and Rogawski, 2002).…”

Section: Drugsmentioning

confidence: 99%

Antipsychotic-Like Properties of 5-α-Reductase Inhibitors

Bortolato

Frau

Orrù

et al. 2008

Neuropsychopharmacol

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Recent evidence indicates that neuroactive steroids may participate in the pathogenesis of schizophrenia spectrum disorders, yet the mechanisms of this involvement are elusive. As 5-a-reductase (5AR) is the rate-limiting enzyme of one of the two major metabolic pathways in brain steroidogenesis, we investigated the effects of its blockade in several rat models of psychotic-like behavior. The 5AR inhibitor finasteride (FIN, 60 or 100 mg/kg, intraperitoneal, i.p.) dose-and time-dependently antagonized prepulse inhibition (PPI) deficits induced by apomorphine (APO, 0.25 mg/kg, subcutaneous, s.c.) and d-amphetamine (AMPH, 5 mg/kg, s.c.), in a manner analogous to haloperidol (HAL, 0.1 mg/kg, i.p.) and clozapine (CLO, 5 mg/kg, i.p.). Similar results were observed with the other 5AR inhibitors dutasteride (DUT, 40 or 80 mg/kg, i.p.) and SKF 105111 (30 mg/kg, i.p.). FIN (60 or 100 mg/kg, i.p.) also reduced hyperlocomotion induced by AMPH (1 or 3 mg/kg, s.c.) and attenuated stereotyped behaviors induced by APO (0.25 mg/kg, s.c.). Nevertheless, FIN (100 mg/kg, i.p.) did not reverse the PPI disruption induced by the N-methyl-d-aspartate receptor antagonist dizocilpine (0.1 mg/kg, s.c.). FIN (60-300 mg/kg, i.p.) induced no catalepsy in either the bar test or the paw test. Our results suggest that 5AR inhibitors elicit antipsychotic-like effects in animals and may be proposed as a putative novel target in the management of psychotic disorders.

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“…On the contrary, an increase in excitability was noted following a rapid decline in progesterone (''progesterone withdrawal''; Reddy et al, 2001). However, in the experiments of Reddy et al (2001), allopregnanolone levels were clearly decreased when seizure susceptibility was high.…”

Section: Susceptibility To Statusmentioning

confidence: 99%

Seizure susceptibility in intact and ovariectomized female rats treated with the convulsant pilocarpine

Scharfman

Goodman

Rigoulot

et al. 2005

Experimental Neurology

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Despite numerous neuroendocrinological studies of seizures, the influence of estrogen and progesterone on seizures and epilepsy remains unclear. This may be due to the fact that previous studies have not systematically compared distinct endocrine conditions and included all relevant controls. The goal of the present study was to conduct such a study using pilocarpine as chemoconvulsant. Thus, age and weight-matched, intact or ovariectomized rats were tested to determine incidence of status epilepticus and to study events leading to status. Intact female rats were sampled at each cycle stage (proestrus, estrus, metestrus, or diestrus 2). Convulsant was administered at the same time of day, 10:00-10:30 a.m. Statistical analysis showed that there was a significantly lower incidence of status on the morning of estrus, but differences were attenuated in older animals. Ovariectomized rats were distinct in their rapid progression to status. These results show that the incidence of status in female rats following pilocarpine injection, and the progression to pilocarpineinduced status, are influenced by reproductive state as well as age. The hormonal milieu present specifically on the morning of estrus appears to decrease susceptibility to pilocarpine-induced status, particularly at young ages. In contrast, the chronic absence of reproductive steroids that characterizes the ovariectomized rat leads to a more rapid progression to status. This dissociation between incidence vs. progression provides new insight into the influence of estrogen and progesterone on seizures.

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Neurosteroid Withdrawal Model of Perimenstrual Catamenial Epilepsy

Cited by 145 publications

References 50 publications

Mechanisms of neurosteroid interactions with GABAA receptors

Mechanisms of neurosteroid interactions with GABAA receptors

Antipsychotic-Like Properties of 5-α-Reductase Inhibitors

Seizure susceptibility in intact and ovariectomized female rats treated with the convulsant pilocarpine

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