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Updated: Aug 23, 2026

Assessment of Dopaminergic Homeostasis in Mice by Use of High-performance Liquid Chromatography Analysis and Synaptosomal Dopamine Uptake
Published on: September 21, 2017
The catechol-O-methyltransferase polymorphism: relations to the tonic-phasic dopamine hypothesis and neuropsychiatric
Robert M Bilder1, Jan Volavka, Herbert M Lachman
1Department of Psychiatry, David Geffen School of Medicine and Psychology, UCLA Neuropsychiatric Institute, University of California at Los Angeles, Los Angeles, CA, USA. rbilder@mednet.ucla.edu
Abstract:
Diverse phenotypic associations with the catechol-O-methyltransferase (COMT) Val158Met polymorphism have been reported. We suggest that some of the complex effects of this polymorphism be understood from the perspective of the tonic-phasic dopamine (DA) hypothesis. We hypothesize that the COMT Met allele (associated with low enzyme activity) results in increased levels of tonic DA and reciprocal reductions in phasic DA in subcortical regions and increased D1 transmission cortically. This pattern of effects is hypothesized to yield increased stability but decreased flexibility of neural network activation states that underlie important aspects of working memory and executive functions; these effects may be beneficial or detrimental depending on the phenotype, a range of endogenous factors, and environmental exigencies. The literature on phenotypic associations of the COMT Val158Met polymorphism is reviewed, highlighting areas where this hypothesis may have explanatory value, and pointing to possible directions for refinement of relevant phenotypes and experimental evaluation of this hypothesis.
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