Abstract

Rats with lesions in the medial forebrainbundle demonstrate significant decreases in brain concentrations of serotonin and norepinephrine without showing signs of sedation. Nevertheless, these lesioned animals do demonstrate an increased sensitivity to the sedative action of reserpine as measured by depression of lever pressing for water reward. The present study examined this increased sensitivity toreserpine. For any given dosage of reserpine, rats with medial forebrain bundle lesions demonstrated lower final concentrations of brain amines and an associated greater sedation ascompared with control rats given the same dosage of drug. The greater behavioral sensitivity to reserpine produced by these lesions could be accounted for by the additive effects of drug and lesion on brain amine concentrations. Similar results were obtained by premedication of nonlesioned animals with reserpine. Degree of sedation and brain concentrations of amines were significantly and highly correlated in individual animals at 2,20 and 50 hr after reserpine injection. However, the curve relating sedation to amine concentration was shifted to the rightby 50 hr.