Dopaminergic mechanisms of reduced basal ganglia responses to hedonic reward during interferon alfa administration.

Lucile Capuron, Giuseppe Pagnoni, Daniel F. Drake, Bobbi J. Woolwine, James R. Spivey, Ronald J. Crowe, John R. Votaw, Mark M. Goodman, Andrew H. Miller
Arch Gen Psychiatry. 2012-10-01; 69(10): 1044
DOI: 10.1001/archgenpsychiatry.2011.2094

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1. Arch Gen Psychiatry. 2012 Oct;69(10):1044-53. doi:

Dopaminergic mechanisms of reduced basal ganglia responses to hedonic reward
during interferon alfa administration.

Capuron L(1), Pagnoni G, Drake DF, Woolwine BJ, Spivey JR, Crowe RJ, Votaw JR,
Goodman MM, Miller AH.

Author information:
(1)Laboratory of Nutrition and Integrative Neurobiology, National Institute for
Agricultural Research 1286 – University Victor Segalen Bordeaux, Bordeaux,

CONTEXT: Inflammatory cytokines or cytokine inducers can alter basal ganglia
activity, including reducing responsiveness to rewarding stimuli that may be
mediated by cytokine effects on dopamine function.
OBJECTIVES: To determine whether long-term administration of the inflammatory
cytokine interferon alfa reduces the basal ganglia response to reward and whether
such changes are associated with decreased presynaptic striatal dopamine function
and altered behavior.
DESIGN: Cross-sectional and longitudinal studies.
SETTING: Outpatient research unit and neuroimaging facilities at Emory
University, Atlanta, Georgia.
PATIENTS: Medically stable adults with chronic hepatitis C virus (HCV) infection
eligible for interferon alfa treatment.
MAIN OUTCOME MEASURES: Neural activity in the ventral striatum during a hedonic
reward task as measured by functional magnetic resonance imaging, uptake and
turnover of radiolabeled fluorodopa F 18 (18F-dopa) in caudate and putamen using
positron emission tomography, and interferon alfa-induced depression, anhedonia,
fatigue, and neurotoxicity.
RESULTS: Patients with HCV receiving interferon alfa for 4 to 6 weeks (n = 14)
exhibited significantly reduced bilateral activation of the ventral striatum in
the win vs lose condition of a gambling task compared with patients with HCV
awaiting interferon alfa treatment (n = 14). Reduced activation of the ventral
striatum was, in turn, significantly correlated with anhedonia, depression, and
fatigue. In a separate longitudinal study, patients with HCV treated with
interferon alfa for 4 to 6 weeks (n = 12) exhibited significantly increased
18F-dopa uptake and decreased 18F-dopa turnover in caudate and putamen and in the
same ventral striatal regions identified in the functional magnetic resonance
imaging study. Baseline and percentage change in 18F-dopa uptake and turnover
were correlated with behavioral alterations, including depression, fatigue, and
neurotoxicity, during interferon alfa administration.
CONCLUSIONS: These data replicate and extend findings that inflammatory stimuli,
including inflammatory cytokines, such as interferon alfa, alter basal ganglia
activity and behavior in association with significant changes in presynaptic
striatal dopamine function consistent with decreased dopamine synthesis or

DOI: 10.1001/archgenpsychiatry.2011.2094
PMCID: PMC3640298
PMID: 23026954 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus