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.).
- Baker DA, Cornish JL, Kalivas PW (2002) Glutamate and dopamine interactions in the motive circuit. In: Herman BH (ed) Glutamate and addiction. Humana, Totowa, pp 143–156Google Scholar
- Burns LH, Everitt BJ, Kelley AE, Robbins TW (1994) Glutamate-dopamine interactions in the ventral striatum: role in locomotor activity and responding with conditioned reinforcement. Psychopharmacology 115:516–528Google Scholar
- Carroll ME, Comer SD (1996) Animal models of relapse. Exp Clin Psychopharmacol 4:11–18Google Scholar
- Cornish JL, Kalivas PW (2000) Glutamate transmission in the nucleus accumbens mediates relapse in cocaine addiction. J Neurosci (Online) 20:RC89Google Scholar
- Erb S, Salmaso N, Rodaros D, Stewart J (2001) A role for the CRF-containing pathway from central nucleus of the amygdala to bed nucleus of the stria terminalis in the stress-induced reinstatement of cocaine seeking in rats. Psychopharmacology 158:360–365Google Scholar
- Kalivas PW, McFarland K, See RE (2003b) Psychiatric pathophysiology: addiction. In: Tasman A, Kay J, Lieberman JA (eds) Psychiatry. Wiley, Chichester, pp 330–337Google Scholar
- Kruzich PJ, See RE (2001) Differential contributions of the basolateral and central amygdala in the acquisition and expression of conditioned relapse to cocaine-seeking behavior. J Neurosci 21:RC155:1–5Google Scholar
- Martin JH (1989) Neuroanatomy text and atlas. Elsevier, AmsterdamGoogle Scholar
- Park WK, Bari AA, Jey AR, Anderson SM, Spealman RD, Rowlett JK, Pierce RC (2002) Cocaine administered into the medial prefrontal cortex reinstates cocaine-seeking behavior by increasing AMPA receptor-mediated glutamate transmission in the nucleus accumbens. J Neurosci 22:2916–2925PubMedGoogle Scholar
- Parkinson JA, Olmstead MC, Burns LH, Robbins TW, Everitt BJ (1999) Dissociation in effects of lesions of the nucleus accumbens core and shell on appetitive pavlovian approach behavior and the potentiation of conditioned reinforcement and locomotor activity by d-amphetamine. J Neurosci 19:2401–2411PubMedGoogle Scholar
- Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic, New YorkGoogle Scholar
- Sinha R (2001) How does stress increase risk of drug abuse and relapse? Psychopharmacology 158:343–359Google Scholar
- Weiss F, Maldonado-Vlaar CS, Parsons LH, Kerr TM, Smith DL, Ben-Shahar O (2000) Control of cocaine-seeking behavior by drug-associated stimuli in rats: effects on recovery of extinguished operant-responding and extracellular dopamine levels in amygdala and nucleus accumbens. Proc Natl Acad Sci USA 97:4321–4326PubMedGoogle Scholar