Finasteride Blocks the Reduction in Ictal Activity Produced by Exogenous Estrous Cyclicity

Frye, Cheryl A.; Scalise, Trudy J; Bayon, Laura E.

doi:10.1046/j.1365-2826.1998.00202.x

Cited by 64 publications

(15 citation statements)

References 45 publications

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“…Levels of E 2 and progestins were measured using radioimmunoassay per previous methods (Frye et al, 1996, 1998a,b). Sample tube concentrations were calculated using the logit–log method of Rodbard and Hutt (1974).…”

Section: Methodsmentioning

confidence: 99%

Estrogen is necessary for 5α-pregnan-3α-ol-20-one (3α,5α-THP) infusion to the ventral tegmental area to facilitate social and sexual, but neither exploratory nor affective behavior of ovariectomized rats

Frye

Paris

Rhodes

2008

Pharmacology Biochemistry and Behavior

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The progesterone metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP, allopregnanolone), acts in the ventral tegmental area (VTA) to facilitate exploratory, anti-anxiety, and socio-sexual behavior among ovariectomized (OVX), estrogen (E 2 )-primed rats and gonadally-intact rats with high (proestrus) or low (diestrus) endogenous E 2 levels. The extent to which E 2 is required for these effects of 3α,5α-THP is not known. OVX rats were primed with systemic 17β-estradiol (10 µg) or oil vehicle and were infused 44 h later with 3α,5α-THP (100 ng) or β-cyclodextrin vehicle to the VTA, substantia nigra (SN), or central grey (CG). Rats were assessed in a battery of exploratory (open field), anxiety (elevated plus maze), social (partner preference, social interaction), and sexual (paced mating) tasks. E 2 -priming was necessary for 3α,5α-THP infusions to facilitate social interaction and mating and midbrain 3α,5α-THP levels were higher among E 2 -compared to vehicle-primed rats. Irrespective of E 2 -priming, rats infused with 3α,5α-THP to the VTA, but not SN or CG, demonstrated increased exploration in an open field, anti-anxiety behavior on an elevated plus maze, and preference for a male. Thus, actions of 3α,5α-THP in the VTA to enhance social and sexual behaviors were reliant on E 2 but increases in exploratory and anti-anxiety behavior were not.

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Section: Methodsmentioning

confidence: 99%

Estrogen is necessary for 5α-pregnan-3α-ol-20-one (3α,5α-THP) infusion to the ventral tegmental area to facilitate social and sexual, but neither exploratory nor affective behavior of ovariectomized rats

Frye

Paris

Rhodes

2008

Pharmacology Biochemistry and Behavior

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“…These include pseudopregnancy, chronic progesterone, and progesterone (neurosteroid) withdrawal models (Smith et al, 1998; Moran and Smith, 1998; Reddy et al, 2001). The second category of models is based on the naturally occurring estrous cycle or administration of exogenous hormones that simulate the specific stages of estrous cycle in ovariectomized rats (Frye et al, 1998; Frye and Bayon, 1998). These physiological models better mimic the normal ovarian cycle.…”

Section: Neuroendocrine Mechanisms Of Catamenial Epilepsymentioning

confidence: 99%

Neurosteroids and their role in sex-specific epilepsies

Reddy

2014

Neurobiology of Disease

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Neurosteroids are involved in sex-specific epilepsies. Allopregnanolone and related endogenous neurosteroids in the brain control excessive neuronal excitability and seizure susceptibility. Neurosteroids activate GABA-A receptors, especially extrasynaptic αβδ-GABA-A receptor subtypes that mediate tonic inhibition and thus dampen network excitability. Our studies over the past decade have shown that neurosteroids are broad-spectrum anticonvulsants and confer seizure protection in various animal models. Neurosteroids also exert antiepileptogenic effects. There is emerging evidence on a critical role for neurosteroids in the pathophysiology of the sex-specific forms of epilepsies such as catamenial epilepsy, a menstrual cycle-related seizure disorder in women. Catamenial epilepsy is a neuroendocrine condition in which seizures are clustered around specific points in the menstrual cycle, most often around the perimenstrual or periovulatory period. Apart from ovarian hormones, fluctuations in neurosteroid levels could play a critical role in this gender-specific epilepsy. Neurosteroids also regulate the plasticity of synaptic and extrasynaptic GABA-A receptors in the hippocampus and other regions involved in epilepsy pathology. Based on these studies, we proposed a neurosteroid replacement therapy for catamenial epilepsy. Thus, neurosteroids are novel drug targets for pharmacotherapy of epilepsy.

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“…Mimicking the hormonal phase of proestrus/estrus (with high progesterone administration) in ovariectomized (OVX) rats was associated with increased brain 3á,5á-THP levels and decreased number of partial seizures following perforant pathway stimulation, when compared with low hormonal phases (46). Administration of finasteride reversed the anticonvulsant effects of hormonally simulated estrus, suggesting that metabolism of progesterone to 3á,5á-THP contributed to the anticonvulsant effects of estrus.…”

Section: Animal Models Of Epileptic and Absence Seizuresmentioning

confidence: 99%

A New Look at the 5?-Reductase Inhibitor Finasteride

et al. 2006

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Finasteride is the first 5á-reductase inhibitor that received clinical approval for the treatment of human benign prostatic hyperplasia (BPH) and androgenetic alopecia (male pattern hair loss). These clinical applications are based on the ability of finasteride to inhibit the Type II isoform of the 5á-reductase enzyme, which is the predominant form in human prostate and hair follicles, and the concomitant reduction of testosterone to dihydrotestosterone (DHT). In addition to catalyzing the rate-limiting step in the reduction of testosterone, both isoforms of the 5á-reductase enzyme are responsible for the reduction of progesterone and deoxycorticosterone to dihydroprogesterone (DHP) and dihydrodeoxycorticosterone (DHDOC), respectively. Recent preclinical data indicate that the subsequent 3á-reduction of DHT, DHP and DHDOC produces steroid metabolites with rapid non-genomic effects on brain function and behavior, primarily via an enhancement of ã-aminobutyric acid (GABA)ergic inhibitory neurotransmission. Consistent with their ability to enhance the action of GABA at GABA A receptors, these steroid derivatives (termed neuroactive steroids) possess anticonvulsant, antidepressant and anxiolytic effects in addition to altering aspects of sexual-and alcohol-related behaviors. Thus, finasteride, which inhibits both isoforms of 5á-reductase in rodents, has been used as a tool to manipulate neuroactive steroid levels and determine the impact on behavior. Results of some preclinical studies and clinical observations with finasteride are described in this review article. The data suggest that endogenous neuroactive steroid levels may be inversely re- 53

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Finasteride Blocks the Reduction in Ictal Activity Produced by Exogenous Estrous Cyclicity

Cited by 64 publications

References 45 publications

Estrogen is necessary for 5α-pregnan-3α-ol-20-one (3α,5α-THP) infusion to the ventral tegmental area to facilitate social and sexual, but neither exploratory nor affective behavior of ovariectomized rats

Estrogen is necessary for 5α-pregnan-3α-ol-20-one (3α,5α-THP) infusion to the ventral tegmental area to facilitate social and sexual, but neither exploratory nor affective behavior of ovariectomized rats

Neurosteroids and their role in sex-specific epilepsies

A New Look at the 5?-Reductase Inhibitor Finasteride

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