Effect of Thyrotropin-releasing Hormone on Pentobarbitone-induced Sleep in Rats: Continuous Treatment with a Sustained Release Injectable Formulation

Abstract

Abstract The mode of action and the time course of the effects of continuous thyrotropin-releasing hormone (TRH) treatment using a two-week sustained release injectable formulation of TRH-containing copoly(±)-lactic/glycolic acid) microspheres (TRH-SR) on pentobarbitone-induced sleeping time were studied in rats. Subcutaneous treatment with TRH-SR at doses corresponding to 0·05 and 0·2 mg of TRH kg−1 day−1 caused a dose-related shortening of pentobarbitone-induced sleeping time with a minimum effective dose (MED) of 0·05 mg kg−1 day−1, without affecting the body weight gain. On the other hand, the MED of TRH when given as a bolus subcutaneous injection was 40 mg kg−1. The effect of TRH-SR treatment was blocked by intraperitoneal scopolamine (0·1 mg kg−1) and mecamylamine (2 mg kg−1) but not by scopolamine methyl bromide (0·1 mg kg−1). The results indicate that continuous TRH treatment using TRH-SR causes shortening of pentobarbitone-induced sleeping time at doses lower than those required using bolus injection and probably by a mechanism involving the central cholinergic system.