Cue Reactivity in the Ventral Striatum Characterizes Heavy Cannabis Use, Whereas Reactivity in the Dorsal Striatum Mediates Dependent Use
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Abstract
Background Animal models of addiction suggest that the transition from incentive-driven drug use 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 neural 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 current functional magnetic resonance imaging study examined behavioral and neural cue reactivity in dependent (n = 18) and nondependent (n = 20) heavy cannabis users and a nonusing reference group (n = 44). Results Irrespective of dependence status, cannabis users demonstrated elevated trait impulsivity as well as increased ventral striatal reactivity and striatal frontal coupling in response to drug cues. Dependent users selectively exhibited dorsal striatal reactivity and decreased striatal limbic coupling during cue exposure. An exploratory analysis revealed that higher ventral caudate neural cue reactivity was associated with stronger cue-induced arousal and craving in dependent users, whereas this pattern was reversed in nondependent users. Conclusions Taken together, the current findings suggest that exaggerated responses 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.
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The increased dorsal striatum activity may reflect a shift from ventral striatum involvement in early stages of behavioral addictions to dorsal striatum involvement in later stages when the behavior becomes more habitual.
“The fi ndings may re fl ect shifts from involvement of the ventral striatum in early stages of behavioral addictions when being confronted with addiction-related stimuli to involvement of the dorsal striatum in later stages of the disorder, when the behavior becomes more habitual (Everitt and Robbins, 2013, 2016; Zhou et al., 2019).”
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Self-citation
- Authors
- Zhou, X., Zimmermann, K., Xin, F., Zhao, W., Derckx, R. T., Sassmannshausen, A., Scheele, D., Hurlemann, R., Weber, B., Kendrick, K. M., & Becker, B.
- Affiliations
- University of Electronic Science and Technology of China (CN)
- University of Bonn (DE)
- Corresponding author
- Becker, Benjamin
- Venue
- Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
- Publisher
- Elsevier BV
- Published
- 2019-08
- Volume
- 4
- Issue
- 8
- Pages
- 751-762
- ISSN
- 2451-9022 (ISSN-L)
- OpenAlex
- W2952767082
- Cited by
- 77
- References
- 91
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 8 · 2023: 10 · 2022: 11 · 2021: 18 · 2020: 14 · 2019: 2
- FWCI
- 6.81
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Biological Psychiatry Cognitive Neuroscience and Neuroimaging (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (NSFC) (91632117, 31530032 [to KKM)
- Fundamental Research Funds (ZYGX2015Z002 [to BB])
- Department of Sichuan Province (2018JY0001 [to BB])
- German Research Foundation (BE5465/2-1, HU1302/4-1 [to RH])
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- cannabis use disorder, cue reactivity, ventral striatum, dorsal striatum, trait impulsivity, drug-seeking behavior, habit formation, caudate nucleus, craving
- MeSH terms
- Adult, Brain, Brain Mapping, Marijuana Abuse, Caudate Nucleus, Cues, Frontal Lobe, Humans, Impulsive Behavior, Magnetic Resonance Imaging, Male, Marijuana Smoking, Neural Pathways, Young Adult, Ventral Striatum
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