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The Journal of Neuroscience, October 1, 2000, 20(19):7489-7495
Dissociation in Conditioned Dopamine Release in the Nucleus
Accumbens Core and Shell in Response to Cocaine Cues and during
Cocaine-Seeking Behavior in Rats
Rutsuko
Ito,
Jeffrey W.
Dalley,
Simon R.
Howes,
Trevor
W.
Robbins, and
Barry J.
Everitt
Department of Experimental Psychology, University of Cambridge,
Cambridge CB2 3EB, United Kingdom
The dopaminergic innervation of the nucleus accumbens is generally
agreed to mediate the primary reinforcing and locomotor effects of
psychostimulants, but there is less consensus on conditioned dopamine
(DA) release during drug-seeking behavior. We investigated the
neurochemical correlates of drug-seeking behavior under the control of
a drug-associated cue [a light conditioned 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 one of two
identical levers led to an intravenous cocaine infusion (0.25 mg/infusion) and a 20 sec light CS+. Response requirements for cocaine
and the CS+ were then progressively increased until stable responding
was established under a second-order schedule of reinforcement. During
microdialysis, rats 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 intravenous cocaine
self-administration; (2) noncontingent presentations of a
cocaine-associated CS+ led to increased DA release selectively in the
nucleus accumbens core; and (3) extracellular DA levels were unaltered
in both core and shell during a protracted period of drug-seeking
behavior under the control of the same cocaine-associated cue. These
results indicate that the mesolimbic dopamine system is activated after
exposure to drug-associated stimuli under specific conditions.
Key words:
cocaine; dopamine; nucleus accumbens; second-order
schedule; conditioned reinforcement; microdialysis
Copyright © 2000 Society for Neuroscience 0270-6474/00/20197489-07$05.00/0
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