Cue Reactivity in the Ventral Striatum Characterizes Heavy Cannabis Use, Whereas Reactivity in the Dorsal Striatum Mediates Dependent Use

Abstract

Background Animal models of addiction suggest that the transition from incentive-driven to habitual and ultimately compulsive drug use is mediated by a shift from ventral to dorsal striatal cue-control over drug seeking. Previous studies in human cannabis users reported elevated trait impulsivity and cue-reactivity in striatal circuits, however, these studies were not able to separate addiction-related from exposure-related adaptations.Methods To differentiate the adaptive changes, the present functional magnetic resonance imaging study examined behavioral and neural cue-reactivity in dependent (n = 18) and nondependent (n = 20) heavy cannabis users and a non-using reference group (n = 44). ResultsIrrespective of dependence status, cannabis users demonstrated elevated trait impulsivity as well as increased ventral striatal reactivity and striato-frontal coupling in response to drug cues. Dependent users selectively exhibited dorsal-striatal reactivity and decreased striato-limbic coupling during cue-exposure. An exploratory analysis revealed that higher ventral caudate cue-reactivity was associated with stronger cue-induced arousal and craving in dependent users, whereas this pattern was reversed in non-dependent users.Conclusions Together the present findings suggest that an incentive sensitization of the ventral striatal reward system may promote excessive drug use in humans, whereas adaptations in dorsal striatal systems engaged in habit formation may promote the transition to addictive use.

Common and separable neural alterations in substance use disorders: evidence from coordinate-based meta-analyses of functional neuroimaging studies in human

“…Accordingly, alterations in this region may reflect adaptations in incentive-based learning processes that promote exaggerated salience attributed to the drug as well as deficits in controlling impulsive behavior. The dorsal striatum, on the other hand, has been strongly associated with habit learning and the transition from reward-driven to compulsive behavior in addiction [15], [16], [142] and may promote the development of compulsive drug use in the context of progressive loss of behavioral control [143]. Together, these findings emphasize that separable neural systems may mediate specific behavioral dysregulations…”

Shared gray matter alterations in individuals with diverse behavioral addictions: A voxel-wise meta-analysis

“…On the other hand, an interesting finding that decreased GM volume in the dorsal striatum but not in the ventral striatum is enlightening. According to fMRI studies on substance addiction, the activation of ventral striatal reward system was associated with excessive drug use at an early stage while dorsal part dominated after the formation of habitual behaviors (Vollstadt-Klein et al, 2010;X. Zhou et al, 2019b), indicating the transition from heavy use to dependence is probably mediated by a functional ventral-dorsal shift.…”

Convergent cross-sectional and longitudinal evidence for gaming-cue specific posterior parietal dysregulations in early stages of Internet Gaming Disorder

“…Cue-reactivity and emotional processing was assessed using a modified version of a fMRI block-design paradigm that has been previously demonstrated to be sensitive to substance dependence and gaming associated neural changes. 15,20,29 is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint…”

“…18.20018036 doi: medRxiv preprint 6 been observed in regular, non-dependent, drug users whereas dependent users during later stages of the disorder exhibit pronounced reactivity in the dorsal striatum engaged in habit formation. [15][16][17] A recent framework by Brand et al extended previous models on substance-related addictions to internet-related addictive behaviors, including gaming, and emphasized the importance to account for interactions of person-affect-cognition and execution variables (I-PACE). 18 A recent update of this model emphasized the relevance to (1) consider predisposing vulnerability factors such as emotional dysregulations, e.g.…”

“…https://doi.org/10.1101/2020.01. 18.20018036 doi: medRxiv preprint 7 23 the important role of ventral striatal cue reactivity during early as well as later stages of substance use disorders has been established 15,24,25 , whereas previous studies on cue-reactivity in IGD revealed inconsistent findings and due to the crosssectional retrospective design remain limited with respect to determining cueassociated changes during the early stages of excessive, regular gaming.…”