This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Although the cerebellum is increasingly being viewed as a brain area involved in cognition, it typically is excluded from circuitry considered to mediate stimulant-associated behaviors since it is low in dopamine. Yet, the primate cerebellar vermis (lobules II-III and VIII-IX) has been reported to contain axonal dopamine transporter immunoreactivity (DAT-IR). We hypothesized that DAT-IR-containing vermis areas would be activated in cocaine abusers by cocaine-related cues and, in healthy humans, would accumulate DAT-selective ligands. We used BOLD fMRI to determine whether cocaine-related cues activated DAT-IR-enriched vermis regions in cocaine abusers and positron emission tomography imaging of healthy humans to determine whether the DAT-selective ligand ((11)C)altropane accumulated in those vermis regions. Results: Cocaine-related cues selectively induced BOLD activation in lobules II-III and VIII-IX in cocaine users, and, at early time points after ligand administration, we found appreciable ((11)C)altropane accumulation in lobules VIII-IX, possibly indicating DAT presence in this region. Discussion: These data suggest that parts of cerebellar vermis mediate cocaine's persisting and acute effects. In light of prior findings illustrating vermis connections to midbrain dopamine cell body regions, established roles for the vermis as a locus of sensorimotor integration and motor planning, and findings of increased vermis activation in substance abusers during reward-related and other cognitive tasks, we propose that the vermis be considered one of the structures involved in cocaine- and other incentive-related behaviors.
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