Abstract:
IMPORTANCE:Cocaine addiction is associated with altered resting-state functional connectivity among regions of the mesocorticolimbic dopamine pathways. Methylphenidate hydrochloride, an indirect dopamine agonist, normalizes task-related regional brain activity and associated behavior in cocaine users; however, the neural systems-level effects of methylphenidate in this population have not yet been described. OBJECTIVE:To use resting-state functional magnetic resonance imaging to examine changes in mesocorticolimbic connectivity with methylphenidate and how connectivity of affected pathways relates to severity of cocaine addiction. DESIGN:Randomized, placebo-controlled, before-after, crossover study. SETTING:Clinical research center. PARTICIPANTS:Eighteen nonabstaining individuals with cocaine use disorders. INTERVENTIONS:Single doses of oral methylphenidate (20 mg) or placebo were administered at each of 2 study sessions. At each session, resting scans were acquired twice: immediately after drug administration (before the onset of effects [baseline]) and 120 minutes later (within the window of peak effects). MAIN OUTCOMES AND MEASURES:Functional connectivity strength was evaluated using a seed voxel correlation approach. Changes in this measure were examined to characterize the neural systems-level effects of methylphenidate; severity of cocaine addiction was assessed by interview and questionnaire. RESULTS:Short-term methylphenidate administration reduced an abnormally strong connectivity of the ventral striatum with the dorsal striatum (putamen/globus pallidus), and lower connectivity between these regions during placebo administration uniquely correlated with less severe addiction. In contrast, methylphenidate strengthened several corticolimbic and corticocortical connections. CONCLUSIONS AND RELEVANCE:These findings help elucidate the neural systems-level effects of methylphenidate and suggest that short-term methylphenidate can, at least transiently, remodel abnormal circuitry relevant to the pathophysiologic characteristics of cocaine addiction. In particular, the effects of methylphenidate within striatal and cortical pathways constitute a potentially viable mechanism by which methylphenidate could facilitate control of behavior in cocaine addiction.
journal_name
JAMA Psychiatryjournal_title
JAMA psychiatryauthors
Konova AB,Moeller SJ,Tomasi D,Volkow ND,Goldstein RZdoi
10.1001/jamapsychiatry.2013.1129subject
Has Abstractpub_date
2013-08-01 00:00:00pages
857-68issue
8eissn
2168-622Xissn
2168-6238pii
1699378journal_volume
70pub_type
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