The effects of thyrotropin releasing hormone on pentobarbital tolerance

The effects of thyrotropin releasing hormone (TRH) on the responses produced by acute and chronic administration of pentobarbital (PB) were investigated in male Swiss Webster mice. Intraperitoneal injection of TRH antagonized the hypothermic and hypnotic effect of PB (75 mg/kg, i.p.). Pentobarbital hypnosis was also antagonized by TRH in mice rendered tolerant to PB by implantation of a pellet (each containing 75 mg of free acid form of the drug) for two days. Injections of TRH (5 mg/kg) once a day or twice a day for two days did not modify the development of tolerance to the hypothermic and hypnotic effect of PB. It is concluded that TRH can modify only the acute responses of PB in naive and PB-tolerant mice, however, in the dosage regimen used it does not affect the processes involved in the genesis of the tolerant state.