The neurosteroid 3α-hydroxy-5α-pregnan-20-one induces catalepsy in mice

Intracerebroventricular injection of the neurosteroid 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha THP) induced catalepsy in mice, within less than 10 min of its administration, which lasted for more than 3 h. This catalepsy was reversed by i.p. administration of picrotoxin, bicuculline, bromocriptine and levodapa-plus-carbidopa combination. A low i.p. dose of 3 alpha,5 alpha THP (1.5 mg/kg) did not induce catalepsy. However, significant catalepsy was noted when 3 alpha,5 alpha THP (1.5 mg/kg) was administered by the i.p. route in the mice pretreated with subcataleptic doses of haloperidol, muscimol or aminooxyacetic acid, The results, for the first time, demonstrate the cataleptogenic potential of 3 alpha,5 alpha THP and suggest that neurosteroids may affect central dopaminergic transmission through their direct action on GABA(A) receptors. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.