PharmacologyBiochemistryand Behavior, Vol. 46, pp. 581-586, 1993 0091-3057/93 $6.00 + .00 Printed in the U.S.A. All fights reserved. Copyright© 1993PergamonPress Ltd. The Role of Nucleus Accumbens Dopamine in Responding on a Continuous Reinforcement Operant Schedule: A Neurochemical and Behavioral Study L. D. McCULLOUGH, M. S. COUSINS AND J. D. SALAMONE ~ Department of Psychology, University of Connecticut, Storrs, CT 06269-1020 Received 27 January 1993 McCULLOUGH, L. D., M. S. COUSINS AND J. D. SALAMONE. The role of nucleus accumbens dopamine in re- sponding on a continuous reinforcement operant schedule: ,4 neurochemical and behavioral study. PHARMACOL BIO- CHEM BEHAV 46(3) 581-586, 1993.-Two experiments were undertaken to investigate the role of nucleus accumbens dopamine (DA) in intrumental lever pressing on a continuous reinforcement (CRF) schedule. Rats trained to press a lever for food reinforcement on a CRF schedule, and food-deprived control rats, were implanted with dialysis probes in the nucleus accumbens. The day after implantation, rats were tested and dialysis samples were assayed for DA and the DA m~tabolite 3,4-dihydroxyphenylacetic acid (DOPAC). Performance of the lever-pressing task resulted in significant increases in ¢xtracel- lular levels of DA and DOPAC relative to control rats. The increases in extracellular DA were significantly correlated (r = 0.92) with the number of lever press responses committed. In the second experiment, the neurotoxic agent 6-hydroxydopamine was infused directly into the nucleus accumbens to investigate the effects of DA depletion on lever-pressing performance. DA depletion had only a modest effect on the total number of lever presses, and there was a significant effect on total lever presses only on the first test day (third day postsurgery). Analyses also were performed on responding across the 45-min session by breaking down the session into three 15-min periods. There was a significant group x time interaction, with DA-depleted rats showing a significant reduction in the numbers of responses in the first 15-min period, but no significant effects over the second or third 15 min in the session. This initial slowing of response rate was present across all 5 test days. These results indicate that DA release and metabolism increases in rats performing on a CRF schedule, and that DA depletion produces a slowing of initial response rate. Nucleus accumbens Dopamine Motivation Operant behavior Microdialysis Behavioral activation ALTHOUGH considerable evidence indicates that dopamine (DA) is involved in the performance of appetitively motivated behavior, the precise behavioral functions performed by DA systems remain uncertain. There is general agreement that sys- temic administration of DA antagonists impairs various in- strumental responses that are supported by positive rein- forcers [for reviews see (27,29,30,40)]. Because interference with DA systems can have such pronounced effects on posi- tively reinforced responses, it has been suggested that DA systems are important for mediating the hedonic effects of rewarding stimuli (40-42). DA in nucleus accumbens has re- ceived particular emphasis in regards to the hypothesized involvement of DA in appetitive motivation (6,12). Yet despite the evidence linking accumbens DA with reinforcement pro- cesses, there have been very few studies focussing on the role of accumbens DA in responding on a continuous reinforce- ment (CRF) schedule for food reinforcement. It is important to examine the role of accumbens DA in the performance of CRF responding, because this schedule represents a funda- mental reinforcement condition in which there is primary posi- tive reinforcement that involves a natural reinforcer. It was observed that rats pressing a lever to receive food on a CRF schedule showed increases in extracellular DA in nucleus ac- cumbens as measured by in vivo microdialysis (12). In that experiment, no correlations between neurochemical and be- havioral data were reported, and it was not clear how the increases in DA release were related to behavioral perfor- mance. Thus, the first experiment of the present series in- volved implantation of dialysis probes into the nucleus accum- bens of rats trained to press a lever on a CRF schedule for food reinforcement, to determine how behavioral perfor- mance was related to changes in DA release or metabolism in i To whom requests for reprints should be addressed. 581