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Psychopharmacology (Berl). 2011 Dec;218(3):533-42. doi: 10.1007/s00213-011-2345-x. Epub 2011 May 20.

Contingent negative variation as a dopaminergic biomarker: evidence from dose-related effects of methylphenidate.

Author information

1
Department of Neuropsychology & Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, PO Box 616, 6200 MD Maastricht, the Netherlands. anke.linssen@maastrichtuniversity.nl

Abstract

RATIONALE:

The basal ganglia play an important role in motor control, which is dependent on dopaminergic input. Preparation of a motor response has been associated with dopamine release in the basal ganglia, and response readiness may therefore serve as a pharmacodynamic marker of dopamine activity.

METHODS:

We measured response readiness using the amplitude of the contingent negative variation (CNV), a slow negative shift in the electroencephalogram. The CNV is evoked in a paradigm in which a warning stimulus (S1) signals the occurrence of the imperative stimulus (S2) 4 s later, to which the participant has to respond. CNV was assessed in healthy volunteers after administration of placebo or 10, 20 or 40 mg of methylphenidate, a catecholamine re-uptake blocker which primarily enhances the synaptic concentration of dopamine and to a lesser extent also noradrenaline. In addition, participants filled out two visual analogue scales measuring subjective ratings of mood and alertness: Profile of Mood States and Bond and Lader.

RESULTS:

Methylphenidate dose dependently increased CNV amplitude and decreased reaction times. Furthermore, participants reported improved mood, feeling more alert, vigorous and content and less angry and tired after methylphenidate.

CONCLUSIONS:

These results indicate that dopamine availability increases response readiness as measured by the CNV paradigm. The CNV appears to be a good candidate biomarker for assessing changes in dopaminergic function by treatments that either directly or indirectly target the dopaminergic system.

PMID:
21597989
PMCID:
PMC3210368
DOI:
10.1007/s00213-011-2345-x
[Indexed for MEDLINE]
Free PMC Article

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