Brain Research, 85 (1975) 13-22 1 3 © Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands EFFECTS OF AMPHETAMINE ISOMERS AND NEUROLEPTICS ON SELF- STIMULATION FROM THE NUCLEUS ACCUMBENS AND DORSAL NOR- ADRENERGIC BUNDLE ANTHONY G. PHILLIPS, SHEILA M. BROOKE AND HANS C. FIBIGER Department of P~ychology and Division of Neurological Sciences, Department of Paychiatry, University of British Columbia, Vancouver (Canada) (Accepted October 10th, 1974) SUMMARY In an attempt to examine the possible role of noradrenergic (NA) and dopamin- ergic (DA) systems in intracranial self-stimulation (ICS), the rate-increasing effects of D- and L-amphetamine on 1CS were determined in rats with nucleus accumbens electrodes (DA placement) or dorsal NA bundle electrodes (NA placement). The D-isomer produced a significantly greater increase in ICS than did the L-isomer in animals with dorsal NA bundle electrodes. In contrast, the amphetamine isomers were equipotent in facilitating ICS in animals with nucleus accumbens electrodes. These data, together with previous observations, suggest that there exists a correlation between equipotential effects of D- and L-amphetamine and DA electrode placements on the one hand, and prepotent effects of D-amphetamine and NA electrode place- ments on the other. Pimozide and haloperidol, which in low doses are thought to specifically block DA receptors, decreased ICS obtained from both DA and NA electrode placements. It is suggested that neuroleptic drugs may produce a general disruption of operant behavior and that the decrease in ICS produced by these agents does not therefore necessarily implicate dopaminergic mechanisms in the neuro- chemistry of reward. INTRODUCI]ON Of the many experimental strategies employed in the study of rewarding intra- cranial self-stimulation (ICS) those focusing on the neurochemical substrates of this phenomenon have received considerable attention in recent years. Although many of the data have been interpreted as being consistent with the noradrenergic (NA)