Enduring scars of cocaine

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Science Translational Medicine  05 Jul 2017:
Vol. 9, Issue 397, eaan8201
DOI: 10.1126/scitranslmed.aan8201


Long-lasting metabolic changes within the brain upon abstinence from cocaine self-administration may increase risk for relapse.

Drug addiction affects hundreds of millions of people worldwide and costs society billions of dollars annually. While neuroimaging studies in humans and preclinical models indicate that persistent structural and functional alterations within dopaminergic reward pathways in the brain may increase risk for enduring and relapsing addiction, no studies to date have assessed longitudinal changes in brain activity after short and long periods of abstinence from drugs of abuse. Investigating such longitudinal changes in brain function during drug withdrawal could shed light on the acute and long-term consequences of drug use for brain processes that may facilitate risk for drug craving and relapse. Nicolas and colleagues designed a study to characterize the effects of withdrawal from short access (mimicking recreational use) and long access (simulating addiction-like use) to voluntary self-administration of cocaine, a widely abused psychostimulant, on brain metabolism in adult male rats.

Researchers studied three groups of rats: (i) drug-naïve (controls), (ii) 1 hour/day (short-access), and (iii) 6 hours/day (long-access) cocaine self-administration for 20 days. All animals then underwent 2-deoxy-2-[18F]fluoro-d-glucose (18FDG) positron emission tomography (PET) imaging scans to assess regional glucose utilization and brain metabolic status after one and four weeks of cocaine abstinence. Data showed that region-specific disruptions in basal metabolic activity were dependent on the extent of cocaine administration and time of abstinence. Furthermore, abstinence from long-access cocaine was associated with longer-lasting neuroadaptations, including decreased glucose utilization in the anterior cingulate and insular cortex and in the dorsolateral striatum, and increased metabolism in the amygdala and hippocampus. These data parallel previously published findings from neuroimaging studies in humans that describe similar disruptions in corticostriatal and limbic brain areas that are associated with addiction and involved in motivation, executive function, stress reactivity, and mood. Although future studies are necessary to replicate these longitudinal findings in humans; characterize how many days of self-administration are necessary to induce these neuroadaptations; and extend the generalizability of the results to females, who are more vulnerable to drug addiction than males, this study highlights persistent changes in brains regions critical for the inhibitory control of behavior that may underlie risk for relapse. Last, these data underscore the existence of invisible scars left by cocaine use, which should be considered in strategies to prevent and manage the social- and self-stigma associated with substance use disorders in our society.

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