Document Detail

Testosterone reduces pentylenetetrazole-induced ictal activity of wildtype mice but not those deficient in type I 5alpha-reductase.
MedLine Citation:
PMID:  11684057     Owner:  NLM     Status:  MEDLINE    
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.
C A Frye; M E Rhodes; A A Walf; J P Harney
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Brain research     Volume:  918     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-10-30     Completed Date:  2002-01-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  182-6     Citation Subset:  IM    
Department of Psychology, University at Albany-SUNY, 1400 Washington Avenue, Albany, NY 12222, USA.
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MeSH Terms
Brain / drug effects*,  enzymology,  physiopathology
Convulsants / pharmacology
Epilepsy / drug therapy*,  enzymology,  physiopathology
Hypogonadism / complications*
Mice, Knockout
Pentylenetetrazole / pharmacology
Reaction Time / drug effects,  physiology
Receptors, Androgen / metabolism
Seizures / chemically induced,  drug therapy*,  enzymology
Testosterone / metabolism*,  pharmacology*
Testosterone 5-alpha-Reductase / deficiency*,  genetics
gamma-Aminobutyric Acid / metabolism
Reg. No./Substance:
0/Convulsants; 0/Receptors, Androgen; 54-95-5/Pentylenetetrazole; 56-12-2/gamma-Aminobutyric Acid; 58-22-0/Testosterone; EC 5-alpha-Reductase

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