The circuitry mediating cocaine-induced reinstatement of drug-seeking behavior

The role of limbic-striato-pallidal circuitry in cocaine-induced reinstatem ent was evaluated. The transient inhibition of brain nuclei associated with motor systems [including the ventral tegmental area (VTA), dorsal prefront al cortex (dPFC), core of the nucleus accumbens (NAcore), and ventral palli dum (VP)] prevented cocaine-induced reinstatement. However, only the VP pro ved to be necessary for food reinstatement, suggesting that the identified circuit is specific to drug-related reinstatement. Supporting the possibili ty that the VTA-dPFC-NAcore-VP is a series circuit mediating reinstatement, simultaneous unilateral microinjection of GABA agonists into the dPFC in o ne hemisphere and into the VP in the contralateral hemisphere abolished coc aine reinstatement. Although dopamine projections from the VTA innervate al l three forebrain nuclei, the blockade of dopamine receptors only in the dP FC antagonized cocaine-induced reinstatement. Furthermore, DA administratio n into the dPFC was sufficient to elicit a reinstatement in drug-related re sponding. These data demonstrate that dopamine release in the dPFC initiate s a dPFC-NAcore-VP series circuit that mediates cocaine-induced drug-seekin g behavior.