Testosterone reduces pentylenetetrazole-induced ictal activity of wildtypemice but not those deficient in type I 5 alpha-reductase

Testosterone's (T) anti-seizure effects may be mediated in part by actions of its 5 alpha -reduced metabolites. To test this hypothesis, T was adminis tered to knockout mice deficient in the 5 alpha -reductase type I enzyme an d wildtype controls and their ictal activity following pentylenetetrazole ( PTZ: 85 mg/kg i.p.) was compared to mice administered vehicle. T to wildtyp e mice increased latencies to forelimb clonus. tonic clonic seizures, hindl imb extension, and death compared to that seen with vehicle administration. Moreover, incidence of tonic clonic seizures and hindlimb extension were r educed in wildtype mice administered T compared to vehicle-administered mic e. T administration to wildtype mice reduced ictal activity compared to T t o knockout mice, which were not different than vehicle-administered control mice. T to wildtype mice increased the latencies and decreased the inciden ce of forelimb clonus compared to T to knockout mice. which were not differ ent from vehicle-administered mice. These data are consistent with T having anti-convulsant effects and that 5 alpha -reduced metabolites may mitigate some of T's anti-seizure effects. (C) 2001 Elsevier Science B.V. All right s reserved.