Pramipexole differentially modulates fronto-striatal circuits in addictive and compulsive disorders.

Introduction: Stimulant use disorder (SUD) and obsessivecompulsive disorder (OCD) are both characterised by compulsive behaviours, previously conceptualised as dysfunctional habits. Thus, imbalanced regulatory control between fronto-striatal and cortico-striatal loops subserving goal-directed and habitual behaviour respectively, possibly involving midbrain dopaminergic input, could be involved in compulsive behaviour. Objectives: We used resting-state fMRI to investigate neural networks of compulsivity in SUD and OCD. We hypothesised that SUD and OCD would differ from healthy volunteers in frontostriatal and cortico-striatal connectivity, and that dopaminergic drug challenges would differentially affect these networks in both disorders. Methods: In a randomised, double-blind, placebo-controlled, crossover design, patients with SUD (n=18), OCD (n=18), and healthy volunteers (n=18) received one dose of placebo, pramipexole, or amisulpride, before undergoing resting-state fMRI. Regions of interest included ventromedial prefrontal cortex (vmPFC), premotor cortex (pMOT) and posterior putamen (pPUT), regions involved in goal-directed and habitual control. We compared functional connectivity within these networks and related connectivity to disorder-specific compulsivity measures. Results: Disorder-specific compulsivity predicted functional connectivity between vmPFC and pPUT on placebo in SUD (r=0.51, p<0.05), but not OCD. Pramipexole reversed this relationship in both disorders, so that the correlation was negative in SUD (r=-0.54, p<0.05), but positive in OCD (r=0.49, p<0.05). Pramipexole equally increased connectivity between vmPFC andpMOT in SUD, and decreased connectivity between pPUT and pMOT in OCD. Conclusions:Our findings suggest that imbalanced fronto-striatal loops are involved in compulsive behaviour in SUD and OCD. Dopaminergic modulation of these circuits putatively contributes to compulsivity, with possible ramifications for novel treatments. Disclosure: Dr Meng is supported by the Wellcome Trust (105602/Z/14/Z) and the NIHR Cambridge Biomedical Research Centre. Dr Bullmore is employed part-time by GSK and part-time by University of Cambridge. He holds stock in GSK. Dr Craig was employed by the University. [ABSTRACT FROM AUTHOR]