Abstinence from cocaine and sucrose self-administration reveals altered mesocorticolimbic circuit connectivity by resting state MRI.

摘要: Previous preclinical studies have emphasized that drugs of abuse, through actions within and between mesocorticolimbic (MCL) regions, usurp learning memory processes normally involved in the pursuit natural rewards. To distinguish MCL circuit pathobiological neuroadaptations accompany addiction from general associated with reward, we trained two groups rats to self-administer either cocaine (IV) or sucrose (orally) followed by an identically enforced 30 day abstinence period. These procedures are known induce behavioral changes neuroadaptations. A third group sedentary animals served as a negative control for handling effects. We examined low-frequency spontaneous fluctuations functional magnetic resonance imaging (fMRI) signal, resting-state connectivity (rsFC), measure intrinsic neurobiological interactions brain regions. Decreased rsFC was seen cocaine-SA compared both sucrose-SA housing prelimbic (PrL) cortex entopeduncular nucleus accumbens core (AcbC) dorsomedial prefrontal (dmPFC). Moreover, individual differences SA escalation predicted strength only Acb-dmPFC circuit. data provide evidence fronto-striatal plasticity across trajectory, which consistent Acb-PFC hypoactivity abstinent human drug addicts, indicating potential level biomarkers may inform therapeutic interventions. They further suggest available cross-sectional reflect consequence rather predispositional predecessor their dependence.