DETERMINATION OF HALOTHANE‐INDUCED SLEEPING TIME IN THE RAT: EFFECT OF PRIOR ADMINISTRATION OF CENTRALLY ACTIVE DRUGS

Abstract

A method is described for the determination of halothane‐induced sleeping time in the rat. The sleeping time exhibited a diurnal variation which was due, at least in part, to a change in the sensitivity of the central nervous system (CNS) to the anaesthetic. Tolerance to halothane did not develop in rats repeatedly exposed to the anaesthetic over a period of over 48 hours. Repeated sleeping time determinations have been used to follow changes in the sensitivity of the CNS to the anaesthetic occurring with time. A tolerance to halothane was induced by pretreatment of rats with doses of amylobarbitone, pentobarbitone or meprobamate sufficient to keep animals anaesthetized for approximately 12 hours. This tolerance was followed by a period of halothane‐hypersensitivity. Halothane‐tolerant animals awakened with higher brain halothane concentrations and were also tolerant to intracerebroventricularly administered pentobarbitone. Halothane‐hypersensitive rats awakened with lower brain halothane concentrations and were also hypersentive to intracerebroventricularly administered pentobarbitone. The possibility that the induction of cross‐tolerance to halothane may be indicative of a drug's potential to produce dependence is discussed. 1976 British Pharmacological Society