Striatal dopamine d2/d3 receptor availability is reduced in methamphetamine dependence and is linked to impulsivity

J Neurosci. 2009 Nov 25;29(47):14734-40. doi: 10.1523/JNEUROSCI.3765-09.2009.

Abstract

While methamphetamine addiction has been associated with both impulsivity and striatal dopamine D(2)/D(3) receptor deficits, human studies have not directly linked the latter two entities. We therefore compared methamphetamine-dependent and healthy control subjects using the Barratt Impulsiveness Scale (version 11, BIS-11) and positron emission tomography with [(18)F]fallypride to measure striatal dopamine D(2)/D(3) receptor availability. The methamphetamine-dependent subjects reported recent use of the drug 3.3 g per week, and a history of using methamphetamine, on average, for 12.5 years. They had higher scores than healthy control subjects on all BIS-11 impulsiveness subscales (p < 0.001). Volume-of-interest analysis found lower striatal D(2)/D(3) receptor availability in methamphetamine-dependent than in healthy control subjects (p < 0.01) and a negative relationship between impulsiveness and striatal D(2)/D(3) receptor availability in the caudate nucleus and nucleus accumbens that reached statistical significance in methamphetamine-dependent subjects. Combining data from both groups, voxelwise analysis indicated that impulsiveness was related to D(2)/D(3) receptor availability in left caudate nucleus and right lateral putamen/claustrum (p < 0.05, determined by threshold-free cluster enhancement). In separate group analyses, correlations involving the head and body of the caudate and the putamen of methamphetamine-dependent subjects and the lateral putamen/claustrum of control subjects were observed at a weaker threshold (p < 0.12 corrected). The findings suggest that low striatal D(2)/D(3) receptor availability may mediate impulsive temperament and thereby influence addiction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amphetamine-Related Disorders / diagnostic imaging
  • Amphetamine-Related Disorders / metabolism*
  • Amphetamine-Related Disorders / physiopathology
  • Basal Ganglia / diagnostic imaging
  • Basal Ganglia / drug effects
  • Basal Ganglia / metabolism
  • Biomarkers / analysis
  • Biomarkers / metabolism
  • Caudate Nucleus / diagnostic imaging
  • Caudate Nucleus / drug effects
  • Caudate Nucleus / metabolism
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism*
  • Dopamine Uptake Inhibitors / adverse effects
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Female
  • Functional Laterality / physiology
  • Humans
  • Image Processing, Computer-Assisted
  • Impulsive Behavior / chemically induced
  • Impulsive Behavior / metabolism*
  • Impulsive Behavior / physiopathology
  • Male
  • Methamphetamine / adverse effects*
  • Neuropsychological Tests
  • Nucleus Accumbens / diagnostic imaging
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Positron-Emission Tomography
  • Putamen / diagnostic imaging
  • Putamen / drug effects
  • Putamen / metabolism
  • Receptors, Dopamine D2 / deficiency*
  • Receptors, Dopamine D2 / drug effects
  • Receptors, Dopamine D3 / deficiency
  • Receptors, Dopamine D3 / drug effects
  • Young Adult

Substances

  • Biomarkers
  • Dopamine Uptake Inhibitors
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Methamphetamine
  • Dopamine