Differential involvement of the core and shell subregions of the nucleus accumbens in conditioned cue-induced reinstatement of cocaine seeking in rats

Psychopharmacology (Berl). 2004 Nov;176(3-4):459-65. doi: 10.1007/s00213-004-1895-6. Epub 2004 May 11.


Rationale: 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.

Objectives: 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.

Methods: 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 microl/side) or vehicle into the NACc or NACs. The effects of these manipulations on locomotor activity were also examined.

Results: 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.

Conclusions: The functional integrity of the NACc, but not the NACs, is necessary for conditioned cue-induced reinstatement of cocaine seeking behavior.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Cocaine / administration & dosage
  • Cocaine-Related Disorders / physiopathology*
  • Cocaine-Related Disorders / psychology*
  • Conditioning, Operant / physiology*
  • Cues*
  • Extinction, Psychological / drug effects
  • Injections
  • Male
  • Motor Activity / drug effects
  • Nucleus Accumbens / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Recurrence
  • Self Administration


  • Cocaine