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

Intracerebroventricular injection of the neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alphaTHP) 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 levodopa-plus-carbidopa combination. A low i.p. dose of 3alpha,5alphaTHP (1.5 mg/kg) did not induce catalepsy. However, significant catalepsy was noted when 3alpha,5alphaTHP (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 3alpha,5alphaTHP and suggest that neurosteroids may affect central dopaminergic transmission through their direct action on GABA(A) receptors.