1. ¹Brain Imaging Center, McLean Hospital, Harvard Medical School, Belmont, MA, USA
2. ²Department of Psychiatry, Division of Neurochemistry, New England Primate Research Center, Harvard Medical School, Southborough, MA, USA
3. ³Division of Nuclear Medicine of the Department of Radiology, Massachusetts General Hospital, Boston, MA, USA
4. ⁴Behavioral Psychopharmacology Research Laboratory, Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA, USA

Correspondence: Dr MJ Kaufman, Brain Imaging Center, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA. Tel: +1 617 855 3469; Fax: +1 617 855 2770; E-mail: kaufman@mclean.harvard.edu

Received 21 March 2005; Revised 25 July 2005; Accepted 2 September 2005; Published online 12 October 2005.

Abstract

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 [¹¹C]altropane accumulated in those vermis regions. 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 [¹¹C]altropane accumulation in lobules VIII–IX, possibly indicating DAT presence in this region. 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.