Dopamine mediation of positive reinforcing effects of amphetamine in stimulant naïve healthy volunteers: results from a large cohort

Eur Neuropsychopharmacol. 2003 Dec;13(6):459-68. doi: 10.1016/j.euroneuro.2003.08.007.

Abstract

A positive experience during a first encounter with a drug of abuse is predictive of subsequent use and might represent a vulnerability factor to develop addiction. This paper presents a meta-analysis of data acquired in 60 healthy volunteers who underwent a low-dose amphetamine challenge (0.3 mg/kg, i.v.) during imaging of dopamine D2 receptor availability with SPECT and the D2/D3 radiotracer [123I]IBZM. Amphetamine-stimulated DA release induced a small, significant and highly variable decrease in striatal D2 receptor availability (-8.3 +/- 6.7%). The magnitude of the decrease in D2 receptor availability was significantly associated with the positive reinforcing effects of the drug reported by the subject (r2 = 0.14, p = 0.003). Age was associated with decreased potency of dopamine to elicit positive reinforcing effects. This study indicates that both a large dopaminergic response and young age during a first encounter with a drug of abuse potential contribute to higher positive reinforcing effects.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Age Factors
  • Amphetamine / pharmacology*
  • Analysis of Variance
  • Benzamides / pharmacokinetics
  • Carbon Isotopes / pharmacokinetics
  • Central Nervous System Stimulants / pharmacology*
  • Cohort Studies
  • Dopamine / metabolism*
  • Emotions
  • Factor Analysis, Statistical
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pyrrolidines / pharmacokinetics
  • Receptors, Dopamine D2 / drug effects
  • Receptors, Dopamine D2 / metabolism*
  • Reinforcement, Psychology*
  • Time Factors
  • Tomography, Emission-Computed, Single-Photon / methods

Substances

  • Benzamides
  • Carbon Isotopes
  • Central Nervous System Stimulants
  • Pyrrolidines
  • Receptors, Dopamine D2
  • 3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide
  • Amphetamine
  • Dopamine