Action of Two Neuroactive Steroids Against Motor Seizures Induced by Pentetrazol in Rats During Ontogeny

P. MAREŠ, R. HAUGVICOVÁ, A. KASAL¹

Institute of Physiology and ¹Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic

Received May 26, 2005
Accepted August 15, 2005
On-line available October 17, 2005

Summary
The anticonvulsant action of two neuroactive steroids, 3α–hydroxy-5β–pregnan-20-one (pregnanolone) and triethylammonium 3α–hydroxy-20-oxo-5α–pregnan-21-yl hydrogensuccinate (THDOC-conjugate), was tested against motor seizures induced by pentetrazol in immature rats. Five age groups (7, 12, 18 and 25 days old and adult rats) were pretreated with the steroids in doses from 2.5 to 40 mg/kg i.p. Twenty minutes later pentetrazol (100 mg/kg s.c.) was administered. Minimal seizures (clonic seizures of head and forelimb muscles with preserved righting ability) could be induced in the three older age groups. They were suppressed by pregnanolone in all these tested groups (this effect was best expressed in 18-day-old rats and decreased with age), whereas significant changes in THDOC-conjugate-pretreated animals appeared only in 18-day-old rats. Generalized tonic-clonic seizures were suppressed by both neuroactive steroids in all age groups, this effect being more marked with pregnanolone and again decreased with age. The 7- and 12-day-old rats exhibited higher sensitivity of the tonic phase so that generalized clonic seizures were observed. Duration of the effect was studied in 12- and 25-day-old animals; it was substantially shorter in the older rats than in 12-day-old animals. Both drugs exhibited an anticonvulsant action in developing rats but, unfortunately, their effect was only shortlasting.


Key words
Convulsions • Rat • Development • Pregnanolone • New neuroactive steroid • Anticonvulsant action • Time course of action