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

J Neurosci. 2013 Mar 6;33(10):4527-35. doi: 10.1523/JNEUROSCI.5261-12.2013.

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Alcoholism / blood
  • Alcoholism / diagnostic imaging
  • Alcoholism / drug therapy
  • Alcoholism / pathology*
  • Analysis of Variance
  • Brain / drug effects
  • Brain / metabolism*
  • Brain Mapping
  • Carbon Radioisotopes / pharmacokinetics
  • Cardiovascular Physiological Phenomena / drug effects
  • Dopamine / metabolism*
  • Dopamine Antagonists / pharmacokinetics
  • Dopamine Uptake Inhibitors / pharmacology
  • Fluorodeoxyglucose F18
  • Humans
  • Male
  • Methylphenidate / blood
  • Methylphenidate / pharmacology
  • Middle Aged
  • Positron-Emission Tomography
  • Raclopride / pharmacokinetics
  • Receptors, Dopamine D2 / metabolism*
  • Regression Analysis
  • Time Factors

Substances

  • Carbon Radioisotopes
  • Dopamine Antagonists
  • Dopamine Uptake Inhibitors
  • Receptors, Dopamine D2
  • Fluorodeoxyglucose F18
  • Methylphenidate
  • Raclopride
  • Dopamine