BEHAVIORALAND NEURALBIOLOGY43, 100-108 (1985) Central Action of Substance P: Possible Role in Reward URSULA STAUBLI Center for the Neurobiology of Learning and Memory, University of California, Irvine California 92717 AND JOSEPH P. HUSTON 1 Institute o f Psychology III, University of Diisseldorf, Universitgitsstrasse 1, D-4000 Diisseldorf, Federal Republic of Germany A series of studies had revealed a dualistic role of post-trial injections of substance P in affecting avoidance behavior depending on the site of the brain in which it is applied. Based on these data, the hypothesis was formulated that substance P has brain site-dependent rewarding and punishing properties, a pos- sibility which was assessed in rats trained on a modified T-maze task. Injections of substance P into the medial forebrain bundle (100 ng) or medial septal nucleus (500 ng) served as a positive reinforcer for conditioned place preference learning in the T maze. Injections into the amygdala (50 ng) or substantia nigra (100 ng) did not have such reinforcing properties. © t985 Academic Press,Inc. A growing body of literature indicates that substance P (SP) is capable of influencing avoidance behavior in rats and mice. These effects have been shown to occur following its peripheral (Hecht, Oehme, Poppei, & Hecht, 1979; Wetzel & Matthies, 1982; Schlesinger, Lipsitz, Peck, & Pelleymounter, 1983; Schlesinger, Lipsitz, Peck, Pelleymounter, Stewart, & Chase, 1983) or central (Huston & St~iubli, 1981; Gaffori, Stewart, & De Wied, 1983) administration. The present study was based on the results of a series of experiments showing brain site-dependent effects of centrally administered SP on avoidance behavior (Huston & Stfiubli, 1981). It was hypothesized that SP may have site-dependent rewarding and aversive properties parallel with its site-dependent facilitative and disruptive effects on memory. Post-trial drug administration was the This work was supported by a grant from the Deutsche Forschungsgesellschaft. We thank W. Buscher for helping analyze the results. Send requests for reprints to Dr. J. Huston. 100 0163-1047/85 $3,00 Copyright© 1985by Academic Press, Inc. All rightsof reproduction in any formreserved.