Article

Cerebellar Vermis Involvement in Cocaine-Related Behaviors

Brain Imaging Center, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.
Neuropsychopharmacology (Impact Factor: 7.83). 07/2006; 31(6):1318-26. DOI: 10.1038/sj.npp.1300937
Source: PubMed

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.

1 Follower
 · 
152 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pavlovian conditioning tunes the motivational drive of drug-associated stimuli, fostering the probability of those environmental stimuli to promote and trigger drug seeking and taking. Interestingly, different areas in the cerebellum are involved in the formation and long-lasting storage of Pavlovian emotional memory. Very recently, we have shown that conditioned preference for an odour associated with cocaine was directly correlated with cFOS expression in cells at the dorsal region of the granule cell layer of the cerebellar vermis. The main goal of the current investigation was to further extend the description of cFOS-IR patterns in cerebellar circuitry after training mice in a cocaine-odour Pavlovian conditioning procedure, including now the major inputs (the inferior olive and pontine nuclei) and one of the output nuclei (the medial deep nucleus) of the cerebellum. The results showed that the cerebellar hallmark of preference towards an odour cue associated to cocaine is an increase in cFOS expression in the dorsal part of the granule cell layer. cFOS-IR levels expressed in the granule cell layer of mice that did not show cocaine conditioned preference did not differ from the basal levels. Remarkably, mice subjected to a random cocaine-odour pairing procedure (the unpaired group) exhibited higher cFOS-IR in the inferior olive, the pontine nuclei and in the deep medial nucleus. Therefore, our findings suggest that inputs and the output of cerebellar circuitry are enhanced when contingency between the CS + and cocaine is lacking.
    Physiology & Behavior 06/2014; 132:24–35. DOI:10.1016/j.physbeh.2014.04.044 · 3.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: While the recent application of brain imaging to study CNS stimulants has offered new insights into the fundamental factors that contribute to their use and abuse, many gaps remain. Brain circuits that mediate pleasure, dependence, craving and relapse are anatomically, neurophysiologically and neurochemically distinct from one another, which has guided the search for correlates of stimulant-seeking and taking behavior. However, unlike other drugs of abuse, metrics for tolerance and physical dependence on stimulants are not obvious. The dopamine theory of stimulant abuse does not sufficiently explain this disorder as serotonergic, GABAergic and glutamagergic circuits are clearly involved in stimulant pharmacology and so tracking the source of the "addictive" processes must adopt a more multimodal, multidisciplinary approach. To this end, both anatomical and functional magnetic resonance imaging (MRI), MR spectroscopy (MRS) and positron emission tomography (PET) are complementary and have equally contributed to our understanding of how stimulants affect the brain and behavior. New vistas in this area include nanotechnology approaches to deliver small molecules to receptors and use MRI to resolve receptor dynamics. Anatomical and blood flow imaging has yielded data showing that cognitive enhancers might be useful adjuncts in treating CNS stimulant dependence, while MRS has opened opportunities to examine the brain's readiness to accept treatment as GABA tone normalizes after detoxification. A desired outcome of the above approaches is being able to offer evidence-based rationales for treatment approaches that can be implemented in a more broad geographic area, where access to brain imaging facilities may be limited.
    Neuropharmacology 07/2014; 87. DOI:10.1016/j.neuropharm.2014.07.011 · 4.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recent emerging functional magnetic resonance imaging (fMRI) studies have identified many brain regions in which gambling cues or rewards elicit activation and may shed light upon the ongoing disputes regarding the diagnostic and neuroscientific issues of gambling disorder (GD). However, no studies to date have systemically reviewed fMRI studies of GD to analyze the brain areas activated by gambling-related cues and examine whether these areas were differentially activated between cases and healthy controls (HC). This study reviewed 62 candidate articles and ultimately selected 13 qualified voxel-wise whole brain analysis studies to perform a comprehensive series of meta-analyses using the effect size-signed differential mapping approach. Compared with HC, GD patients showed significant activation in right lentiform nucleus and left middle occipital gyrus. The increased activities in the lentiform nucleus compared to HC were also found in both GD subgroups that had, or had not, excluded substance use disorder comorbidity. In addition, the South Oaks Gambling Screen scores were associated with hyperactivity in right lentiform nucleus and bilateral parahippocampus, but negatively related to right middle frontal gyrus. These results suggest dysfunction within the frontostriatal cortical pathway in GD, which could contribute to our understanding of the categories and definition of GD and provide evidence for the reclassification of GD as a behavioral addiction in the DSM-5.
    Behavioural Brain Research 09/2014; 275. DOI:10.1016/j.bbr.2014.08.057 · 3.39 Impact Factor

Full-text (3 Sources)

Download
158 Downloads
Available from
May 26, 2014