Differential involvement of the core and shell subregions of the nucleus accumbens in conditioned cue-induced reinstatement of cocaine seeking in rats
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The nucleus accumbens (NAC) is theorized to be a critical element of the neural circuitry that mediates relapse to cocaine seeking. Evidence suggests that the NAC is a functionally heterogeneous structure, and the core (NACc) and shell (NACs) regions of the NAC may play a differential role in stimulus-induced motivated behavior. Thus, determination of the involvement of NAC subregions in conditioned cue-induced reinstatement of cocaine seeking is warranted.
The present study compared the effects of GABA agonist-induced inactivation of the NACc versus NACs on conditioned cue-induced reinstatement of cocaine seeking behavior.
Rats were trained to lever press for cocaine infusions (0.20 mg/infusion, IV) paired with presentations of a light-tone stimulus complex. Responding was then allowed to extinguish prior to reinstatement testing. Reinstatement of cocaine seeking (i.e. responses on the previously cocaine-paired lever) was measured in the presence of response-contingent presentation of the light-tone stimulus complex following microinfusion of muscimol+baclofen (Mus+Bac, 0.1/1.0 mM, respectively, 0.3 μl/side) or vehicle into the NACc or NACs. The effects of these manipulations on locomotor activity were also examined.
Mus+Bac-induced inactivation of the NACc abolished, whereas inactivation of the NACs failed to alter, conditioned cue-induced reinstatement of operant responding relative to vehicle pretreatment. Time course analyses of the effects of these manipulations on locomotion versus operant responding confirmed that the effects of Mus+Bac on reinstatement were not due to suppression of general activity.
The functional integrity of the NACc, but not the NACs, is necessary for conditioned cue-induced reinstatement of cocaine seeking behavior.
KeywordsCocaine Self-administration Extinction Reinstatement Nucleus accumbens Muscimol Baclofen Relapse Conditioned stimuli
The experiments described herein conform to the ethical standards outlined in “Principles of laboratory animal care” (NIH publication no. 80-23, revised 1996). The authors would like to thank the technical assistance of J. Matthew Edwards and William Berglind. This research was supported by National Institute on Drug Abuse grant DA10462 (R.E.S.).
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