Predominance of D2 receptors in mediating dopamine's effects in brain metabolism: Effects of alcoholism

Nora D. Volkow, Dardo Tomasi, Gene Jack Wang, Frank Telang, Joanna S. Fowler, Jean Logan, L. Jayne Maynard, Christopher T. Wong

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Dopamine signals through D1-like and D2-like receptors, which can stimulate or inhibit, respectively, neuronal activity. Here we assessed the balance between D1 or D2 receptor signaling in the human brain and how it is affected in alcoholism. Using PET, we measured the relationship between changes in dopamine and brain glucose metabolism induced by methylphenidate in controls and alcoholics. We show that methylphenidate induced significant DA increases in striatum, amygdala, and medial orbitofrontal cortex, whereas it decreased metabolism in these brain regions. Methylphenidate-induced dopamine increases were greater in controls than in alcoholics, whereas methylphenidate-induced metabolic decreases were greater in alcoholics. For both groups, methylphenidate-induced dopamine increases were associated with decreases in regional brain metabolism, and the correlations were strongest in subthalamic nuclei, anterior cingulate, and medial orbitofrontal cortex. These correlations were more extensive and robust and the slopes steeper in alcoholics than in controls despite their attenuated dopamine responses to methylphenidate, which suggests an impaired modulation of dopamine signals in the brain of alcoholic subjects. These findings are consistent with a predominant inhibitory effect of dopamine in the human brain that is likely mediated by the prominence of dopamine D2/D3 receptors.

Original languageEnglish
Pages (from-to)4527-4535
Number of pages9
JournalJournal of Neuroscience
Volume33
Issue number10
DOIs
StatePublished - 6 Mar 2013
Externally publishedYes

Fingerprint

Dive into the research topics of 'Predominance of D2 receptors in mediating dopamine's effects in brain metabolism: Effects of alcoholism'. Together they form a unique fingerprint.

Cite this