title: Dopamine mediation of positive reinforcing effects of amphetamine in stimulant naïve healthy volunteers: results from a large cohort.
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.
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY, USA.
authors.forename: Anissa
authors.initials: A
authors.lastname: Abi-Dargham
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Kegeles
authors.forename: Diana
authors.initials: D
authors.lastname: Martinez
authors.forename: Robert B
authors.initials: RB
authors.lastname: Innis
authors.forename: Marc
authors.initials: M
authors.lastname: Laruelle
mesh_terms: D000328:Adult; D000367:Age Factors; D000661:Amphetamine / Q000494:pharmacology*; D000704:Analysis of Variance; D001549:Benzamides / Q000493:pharmacokinetics; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D015331:Cohort Studies; D004298:Dopamine / Q000378:metabolism*; D004644:Emotions; D005163:Factor Analysis, Statistical; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D012054:Reinforcement, Psychology; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D001549:Benzamides; D002247:Carbon Isotopes; D000697:Central Nervous System Stimulants; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D000661:Amphetamine; D004298:Dopamine