An α-noradrenergic substrate of rewarding intracranial stimulation (ICS) has been hypothesized based on the observation that the α-antagonist phentolamine produced an inhibition of self-stimulation. The present experiment investigated the effects on hypothalamic self-stimulation of the alpha agonist clonidine in normal and in catecholamine-depleted rats. Using a shuttle-box technique that provides a rate-independent index of the rewarding and aversive components of ICS, it was demonstrated that clonidine produces a dose-dependent inhibition of reward that is clearly dissociable from any non-specific effects of the drug. The ineffectiveness of the peripheral α-agonist 1-phenylephrine indicates that the inhibition of reward produced by clonidine is mediated centrally. Clonidine and the catecholamine synthesis inhibitor α-methyl-p-tyrosine act together in a synergistic manner to greatly increase the magnitude and prolong the duration of the inhibition of reward while leaving the aversive component unaffected. These data are interpreted as supporting an α-noradrenergic basis of ICS reward while indicating that the aversive component of ICS is essentially independent of noradrenergic transmission. © 1976.
Hunt, G. E., Atrens, D. M., Chesher, G. B., & Becker, F. T. (1976). α-Noradrenergic modulation of hypothalamic self-stimulation: Studies employing clonidine, 1-phenylephrine and α-methyl-p-tyrosine. European Journal of Pharmacology, 37(1), 105–111. https://doi.org/10.1016/0014-2999(76)90013-3