Abstinence from cocaine and sucrose self-administration reveals altered mesocorticolimbic circuit connectivity by resting state MRI.
Brain Connectivity. 2014-09-01; 4(7): 499-510
DOI: 10.1089/brain.2014.0264
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1. Brain Connect. 2014 Sep;4(7):499-510. doi: 10.1089/brain.2014.0264.
Abstinence from cocaine and sucrose self-administration reveals altered
mesocorticolimbic circuit connectivity by resting state MRI.
Lu H(1), Zou Q, Chefer S, Ross TJ, Vaupel DB, Guillem K, Rea WP, Yang Y, Peoples
LL, Stein EA.
Author information:
(1)1 Neuroimaging Research Branch, National Institute on Drug Abuse, National
Institutes of Health , Baltimore, Maryland.
Previous preclinical studies have emphasized that drugs of abuse, through actions
within and between mesocorticolimbic (MCL) regions, usurp learning and memory
processes normally involved in the pursuit of natural rewards. To distinguish MCL
circuit pathobiological neuroadaptations that accompany addiction from general
learning processes associated with natural reward, we trained two groups of rats
to self-administer either cocaine (IV) or sucrose (orally) followed by an
identically enforced 30 day abstinence period. These procedures are known to
induce behavioral changes and neuroadaptations. A third group of sedentary
animals served as a negative control group for general handling effects. We
examined low-frequency spontaneous fluctuations in the functional magnetic
resonance imaging (fMRI) signal, known as resting-state functional connectivity
(rsFC), as a measure of intrinsic neurobiological interactions between brain
regions. Decreased rsFC was seen in the cocaine-SA compared with both sucrose-SA
and housing control groups between prelimbic (PrL) cortex and entopeduncular
nucleus and between nucleus accumbens core (AcbC) and dorsomedial prefrontal
cortex (dmPFC). Moreover, individual differences in cocaine SA escalation
predicted connectivity strength only in the Acb-dmPFC circuit. These data provide
evidence of fronto-striatal plasticity across the addiction trajectory, which are
consistent with Acb-PFC hypoactivity seen in abstinent human drug addicts,
indicating potential circuit level biomarkers that may inform therapeutic
interventions. They further suggest that available data from cross-sectional
human studies may reflect the consequence of rather a predispositional
predecessor to their dependence.
DOI: 10.1089/brain.2014.0264
PMCID: PMC4146381
PMID: 24999822 [Indexed for MEDLINE]