Handling of intraperitoneal injections of saline, twice daily for 10 days, did not significantly affect the resting level of corticosterone in the plasma or the adrenals. The conditioning abolished the usual changes in corticosterone levels caused by further handling or injections, reduced the response to exposure to ether vapour and had no effect on the response to histamine. The effect of pentobarbitone on plasma and adrenal corticosterone concentrations was found to be dependent upon the state of the pituitary-adrenal system before administration. Pentobarbitone had no effect on the responses of the adrenal cortex to exogenous adrenocorticotrophin. The responses to ether vapour or histamine of normal rats and rats lightly sedated with pentobarbitone were not significantly different as judged by changes in plasma and adrenal corticosterone concentrations and adrenal ascorbic acid depletion. However, rats deeply anaesthetized with pentobarbitone gave responses indicative of a depression of pituitary-adrenal activity. The sites of action of pentobarbitone on the pituitary-adrenal system are discussed.
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