PREGNENOLONE SULFATE AND PREGNENOLONE DO NOT INTERACT WITH 5-BETA-PREGNANOLONE-INDUCED AND HEXOBARBITONE-INDUCED ANESTHESIA IN THE RAT

We have studied the interaction of pregnenolone sulphate and pregnenol one with 5 beta-pregnanolone- and hexobarbitone-induced anaesthesia in male rats using an EEG threshold method. Burst suppression of the EEG of 1 s or more (''silent second'' (SS)), was used as a criterion of d eep anaesthesia. The effects of the steroid solvents albumin and beta- cyclodextrin were assessed by dose-response curves. Despite a signific ant increase in hexobarbitone threshold dose in relation to increased doses of albumin, there was no correlation between albumin dose and he xobarbitone concentrations in serum, fat and brain tissues. There was no significant difference in threshold concentrations of hexobarbitone between controls given albumin and those pretreated with pregnenolone . In subsequent experiments, 20% beta-cyclodextrin was used as steroid solvent and its volume was maintained at less than 3.0 ml kg(-1) duri ng pretreatment. Neither pregnenolone sulphate nor pregnenolone signif icantly altered the potency of 5 beta-pregnanolone for induction of an aesthesia. Furthermore, there was no interaction of pregnenolone sulph ate and pregnenolone on induction of anaesthesia when hexobarbitone wa s used for anaesthesia.