A MICRODIALYSIS STUDY OF NUCLEUS ACCUMBENS CORE AND SHELL DOPAMINE DURING OPERANT RESPONDING IN THE RAT J. D. SOKOLOWSKI,² A. N. CONLAN and J. D. SALAMONE* Department of Psychology, University of Connecticut, Storrs, CT 06269-1020, U.S.A. Abstract––This investigation examined dopamine release and metabolism in nucleus accumbens core and shell during three operant tasks in the rat. Rats were trained to lever press on a fixed-ratio 5, variable-interval 30 s, or a tandem variable interval 30/fixed-ratio 5 schedules; these three schedules were chosen because they generate a wide range of response and reinforcement rates. After several weeks of training, dialysis probes were implanted into nucleus accumbens core or shell subregions. A single 30 min behavioural session was conducted during the dialysis test session. Rats lever pressing on each of the three operant schedules showed a significant increase in extracellular dopamine relative to the food-deprived control group during the behavioural session. In addition, increases in dopamine in nucleus accumbens shell were found to be significantly greater than in the core during the lever pressing period. Across all three schedules, extracellular dopamine in the nucleus accumbens was significantly correlated with the number of lever presses performed, but was not correlated with the number of food pellets delivered. Analysis of covariance, which used amount of food consumed as the covariate, showed an overall group difference, indicating that dopamine levels increased in lever pressing animals even if one corrected for the amount of food consumed. These results indicate that dopamine release was more responsive in the nucleus accumbens shell than in the core during operant responding, and that increases in extracellular dopamine in nucleus accumbens are related to response rate rather than reinforcement magnitude.  1998 IBRO. Published by Elsevier Science Ltd. Key words: reinforcement, motivation, motor, dialysis, release, lever pressing. Several recent investigations have employed in vivo microdialysis methods to study extracellular levels of neurotransmitters in awake animals (see review in Ref. 33). A number of behavioural conditions, including sexual behaviour, stress, and operant responding are accompanied by increases in accumbens dopamine (DA) release. In male rats exposed to castrated females, DA levels remained constant; however, when exposed to stimuli associ- ated with a receptive female 8 or when mating with receptive females, nucleus accumbens DA signifi- cantly increased. 8,10 Similarly, extracellular DA levels in the nucleus accumbens of female rats is also increased during copulation. 28 Several different stressful stimuli, including tail pinch, footshock, and immobilization and anxiogenic drugs increase nucleus accumbens DA release. 1,14,24 Studies of the effects of food consumption on nucleus accumbens DA release have generated conflicting results, with some studies showing increases, 37,38 while others reported no significant effect. 6,7,25,34 Scheduled pres- entation of small food pellets, which generates con- siderable motor activity, was observed to result in an increase in extracellular DA in accumbens. 25 Lever pressing for food has consistently been shown to produce increases in nucleus accumbens DA activity. 11,19,23,33,34 Several of the previous studies of accumbens DA release during lever press- ing involved placements of dialysis probes into a single site adjacent to the anterior commissure (1.4 mm from midline; see Refs 23, 24, 25, 26 and 34). However, recent anatomical studies have demon- strated that the nucleus accumbens is divided into distinct subregions. 3,4,27,40,41 The region that sur- rounds the anterior commissure is known as the ‘‘core’’, while the ‘‘shell’’ is a crescent-shaped region that is medial and ventral to the core. Several studies have investigated the involvement of core and shell regions of accumbens in various behavioural func- tions, including stress, 9,13,17 locomotor activity, 12,31 self-stimulation, 15 feeding, 21,22 and lever pressing. 36 A few of these investigations have focussed on DA release or metabolism in core and shell of nucleus accumbens. The shell, but not the core, was demon- strated to be responsive to stressors such as restraint, footshock, and an anxiogenic beta carboline. 9,13,17 It also has been suggested that the core and shell play different roles in the a ffective perception of stimuli. 5 *To whom correspondence should be addressed. ²Present address: Department of Pharmacological and Physiological Sciences, University of Chicago, Chicago IL 60637, U.S.A. A bbreviations: DA, dopamine; FR, fixed ratio; TTX, tetro- dotoxin; VI, variable interval. Pergamon N euroscience Vol. 86, No. 3, pp. 1001–1009, 1998 Copyright  1998 IBRO. Published by Elsevier Science Ltd Printed in Great Britain. All rights reserved 0306–4522/98 $19.00+ 0.00 PII: S0306-4522(98)00066-9 1001