The circuitry mediating cocaine-induced reinstatement of drug-seeking behavior.
The role of limbic-striato-pallidal circuitry in cocaine-induced reinstatement was evaluated. The transient inhibition of brain nuclei associated with motor systems [including the ventral tegmental area (VTA), dorsal prefrontal cortex (dPFC), core of the nucleus accumbens (NAcore), and ventral pallidum (VP)] prevented cocaine-induced reinstatement. However, only the VP proved to be necessary for food reinstatement, suggesting that the identified circuit is specific to drug-related reinstatement. Supporting the possibility that the VTA-dPFC-NAcore-VP is a series circuit mediating reinstatement, simultaneous unilateral microinjection of GABA agonists into the dPFC in one hemisphere and into the VP in the contralateral hemisphere abolished cocaine reinstatement. Although dopamine projections from the VTA innervate all three forebrain nuclei, the blockade of dopamine receptors only in the dPFC antagonized cocaine-induced reinstatement. Furthermore, DA administration into the dPFC was sufficient to elicit a reinstatement in drug-related responding. These data demonstrate that dopamine release in the dPFC initiates a dPFC-NAcore-VP series circuit that mediates cocaine-induced drug-seeking behavior.
McFarland
K
K
Department of Physiology and Neuroscience, Medical University of South Carolina, Charleston, South Carolina 29425, USA. mcfarlk@musc.edu.
Kalivas
P W
PW
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002908:Chronic Disease; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000188:drug therapy / Q000503:physiopathology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018755:GABA Agonists / Q000008:administration & dosage; D058785:GABA-A Receptor Agonists; D058786:GABA-B Receptor Agonists; D005917:Globus Pallidus / Q000187:drug effects / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D012054:Reinforcement, Psychology; D012646:Self Administration; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000503:physiopathology
D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D058786:GABA-B Receptor Agonists; D003042:Cocaine; D004298:Dopamine