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

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 D-2 receptor availability with SPECT and the D-2/D-3 radiotracer [I-123]IBZM. Amphetamine-stimulated DA release induced a small, significant and highly variable decrease in striatal D-2 receptor availability (-8.3 +/- 6.7%). The magnitude of the decrease in D-2 receptor availability was significantly associated with the positive reinforcing effects of the drug reported by the subject (r(2) = 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. (C) 2003 Elsevier B.V./ECNP. All rights reserved.