Role of the striatopallidal pathway in renewal and reacquisition of alcohol seeking.
The ventral pallidum (VP) is a key component of the neural circuitry mediating relapse to drug seeking, but the critical afferent pathways to VP recruited during relapse remain poorly understood. We studied the role of the nucleus accumbens core (AcbC) → VP pathway in ABA renewal and reacquisition of alcohol seeking. Rats received application of adenoviral vectors encoding eYFP, ChR2(H134R), or eNpHr3.0 to AcbC and implantation of fiber optic cannulas into VP to permit photostimulation of AcbC terminals there. Rats were then trained to self-administer alcoholic beer in 1 context (A), extinguished in a second context (B), tested in the extinction (ABB) and training (ABA) contexts, and were then tested for reacquisition of alcoholic beer seeking. There was ABA renewal of alcohol seeking, but neither optogenetic excitation nor inhibition of the AcbC → VP pathway affected this renewal. In contrast, optogenetic inhibition of the AcbC → VP striatopallidal pathway reduced reacquisition of alcohol seeking-measured either by the number of active nosepokes emitted or by the number of alcohol rewards earned and consumed. Moreover, optogenetic excitation of the AcbC → VP striatopallidal pathway increased magazine entries during reacquisition test. This finding shows the importance of the AcbC → VP pathway in controlling relapse when the drug reinforcer is present on test and is consistent with a role for the AcbC → VP pathway in regulating the hedonic or incentive motivational properties of drug reinforcers.