Dissociation in conditioned dopamine release in the nucleus accumbens coreand shell in response to cocaine cues and during cocaine-seeking behavior in rats

The dopaminergic innervation of the nucleus accumbens is generally agreed t o mediate the primary reinforcing and locomotor effects of psychostimulants , but there is less consensus on conditioned dopamine (DA) release during d rug-seeking behavior. We investigated the neurochemical correlates of drug- seeking behavior under the control of a drug-associated cue [a light condit ioned stimulus (CS+)] and to noncontingent presentations of the CS+ in the core and shell subregions of the nucleus accumbens. Rats self-administered cocaine under a continuous reinforcement schedule in which a response on on e of two identical levers led to an intravenous cocaine infusion (0.25 mg/i nfusion) and a 20 sec light CS+. Response requirements for cocaine and the CS+ were then progressively increased until stable responding was establish ed under a second-order schedule of reinforcement. During microdialysis, ra ts were presented noncontingently with a set of 10 sec CS+ and neutral tone stimuli (CS-) before and after a 90 min period during which they responded for cocaine under a second-order schedule. Results showed the following: ( 1) nucleus accumbens DA increased in both the core and shell during intrave nous cocaine self-administration; (2) noncontingent presentations of a coca ine-associated CS+ led to increased DA release selectively in the nucleus a ccumbens core; and (3) extracellular DA levels were unaltered in both core and shell during a protracted period of drug-seeking behavior under the con trol of the same cocaine-associated cue. These results indicate that the me solimbic dopamine system is activated after exposure to drug-associated sti muli under specific conditions.