Effect of thyrotropin-releasing hormone on pentobarbitone-induced sleep in rats: continuous treatment with a sustained release injectable formulation.
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.
Hashimoto
T
T
Research and Development Division, Takeda Chemical Industries Ltd., Osaka, Japan.
Wada
T
T
Fukuda
N
N
Nagaoka
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003692:Delayed-Action Preparations; D008297:Male; D008863:Microspheres; D008969:Molecular Sequence Data; D010276:Parasympatholytics / Q000494:pharmacology; D010424:Pentobarbital / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects*; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*
D003692:Delayed-Action Preparations; D010276:Parasympatholytics; D013973:Thyrotropin-Releasing Hormone; D010424:Pentobarbital