Testosterone reduces pentylenetetrazole-induced ictal activity of wildtype mice but not those deficient in type I 5alpha-reductase.
Testosterone's (T) anti-seizure effects may be mediated in part by actions of its 5alpha-reduced metabolites. To test this hypothesis, T was administered to knockout mice deficient in the 5alpha-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 5alpha-reduced metabolites may mitigate some of T's anti-seizure effects.
Frye
C A
CA
Department of Psychology, University at Albany-SUNY, 1400 Washington Avenue, Albany, NY 12222, USA. cafrye@cnsunix.albany.edu
Rhodes
M E
ME
Walf
A A
AA
Harney
J P
JP
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D003292:Convulsants / Q000494:pharmacology; D004827:Epilepsy / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D005260:Female; D007006:Hypogonadism / Q000150:complications*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010433:Pentylenetetrazole / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D011944:Receptors, Androgen / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D013739:Testosterone / Q000378:metabolism* / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D003292:Convulsants; D011944:Receptors, Androgen; D013739:Testosterone; D005680:gamma-Aminobutyric Acid; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D010433:Pentylenetetrazole