Elsevier

Brain Research

Volume 918, Issues 1–2, 9 November 2001, Pages 182-186
Brain Research

Short communication
Testosterone reduces pentylenetetrazole-induced ictal activity of wildtype mice but not those deficient in type I 5α-reductase

https://doi.org/10.1016/S0006-8993(01)02967-5Get rights and content

Abstract

Testosterone’s (T) anti-seizure effects may be mediated in part by actions of its 5α-reduced metabolites. To test this hypothesis, T was administered to knockout mice deficient in the 5α-reductase type I enzyme and wildtype controls and their ictal activity following pentylenetetrazole (PTZ; 85 mg/kg i.p.) was compared to mice administered vehicle. T to wildtype mice increased latencies to forelimb clonus, tonic clonic seizures, hindlimb extension, and death compared to that seen with vehicle administration. Moreover, incidence of tonic clonic seizures and hindlimb extension were reduced in wildtype mice administered T compared to vehicle-administered mice. T administration to wildtype mice reduced ictal activity compared to T to knockout mice, which were not different than vehicle-administered control mice. T to wildtype mice increased the latencies and decreased the incidence of forelimb clonus compared to T to knockout mice, which were not different from vehicle-administered mice. These data are consistent with T having anti-convulsant effects and that 5α-reduced metabolites may mitigate some of T’s anti-seizure effects.

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Acknowledgements

This research was supported by grants from the Catherine Weldon Donaghue Foundation for Medical Research (96-001), the Whitehall Foundation (96-10), and the National Science Foundation (95-14463; 98-96263).

References (30)

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    It remains to be seen whether these inhibitory effects contribute to their anticonvulsant effects. There are two possible mechanisms by which letrozole might produce antiepileptic effects, either by reducing the levels of proconvulsant hormone estradiol by inhibiting aromatization (Thomas and Yang, 1991) or by directing the pathway to synthesis of DHT via 5α-reductase (Reddy, 2004; Fyre et al. 2001). The latter pathway further yields 3α-androstanediol, which is known to exhibit anticonvulsant action (Fyre et al., 1996; Reddy, 2004) thought to be mediated via action on GABAA receptors.

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