Alcohol dependence is associated with blunted dopamine transmission in the ventral striatum

Biol Psychiatry. 2005 Nov 15;58(10):779-86. doi: 10.1016/j.biopsych.2005.04.044. Epub 2005 Jul 14.

Abstract

Background: A decrease in dopamine type 2 receptors (D2) and mesolimbic dopamine transmission predisposes animals to consume alcohol. This study measured D2 receptors and dopamine transmission in human alcohol-dependent (AD) subjects using positron emission tomography (PET) and [11C]raclopride.

Methods: Fifteen AD and 15 healthy control (HC) subjects were scanned before and after a psychostimulant challenge (amphetamine .3 mg/kg intravenous). The outcome measures for baseline D2 receptor availability were binding potential (BP) and the equilibrium partition coefficient (V3''). Amphetamine-induced [11C]raclopride displacement was measured as the difference in V3'' between the two scans.

Results: [11C]raclopride BP was significantly reduced by 16.6% in the limbic striatum, 19.2% in the associative striatum, and 21.3% in the sensorimotor striatum in AD subjects compared with HC. The alcohol-dependent subjects showed a blunting of amphetamine-induced dopamine release in the limbic striatum: [11C]raclopride displacement was -5.2% +/- 3.6% in AD subjects compared with -13.0% +/- 8.8% in HC. However, no significant difference in [11C]raclopride displacement was seen in the associative (-4.6% +/- 5.8% in AD subjects vs. -6.7 +/- 5.4% in HC) and sensorimotor (-12.3% +/- 7.3% in AD subjects vs. -13.7 +/- 7.5% in HC) subdivisions of the striatum between the two groups.

Conclusions: Alcohol dependence was associated with a decrease in D2 receptors in each striatal subdivision, whereas amphetamine-induced dopamine release was reduced in the limbic striatum only.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Alcoholism / diagnosis*
  • Alcoholism / diagnostic imaging
  • Alcoholism / metabolism*
  • Alcoholism / physiopathology
  • Basal Ganglia / diagnostic imaging
  • Basal Ganglia / metabolism*
  • Basal Ganglia / physiopathology
  • Carbon Radioisotopes
  • Dextroamphetamine / pharmacology
  • Dopamine / metabolism*
  • Dopamine / physiology
  • Female
  • Humans
  • Limbic System / drug effects
  • Limbic System / metabolism
  • Limbic System / physiopathology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Positron-Emission Tomography
  • Raclopride
  • Receptors, Dopamine D2 / drug effects
  • Receptors, Dopamine D2 / metabolism
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*

Substances

  • Carbon Radioisotopes
  • Receptors, Dopamine D2
  • Raclopride
  • Dextroamphetamine
  • Dopamine