title: Conditioned dopamine release in humans: a positron emission tomography [11C]raclopride study with amphetamine.
abstract: Studies in laboratory rodents suggest that previously neutral stimuli repeatedly paired with the administration of drugs of abuse can acquire the ability to increase striatal dopamine release. This conditioned neurochemical response is believed to prompt drug seeking in animals and has been hypothesized to contribute to drug craving and relapse in substance abusers. In the present study, we used positron emission tomography and [11C]raclopride to investigate whether amphetamine-predictive stimuli can elicit striatal dopamine release in humans. Nine healthy male volunteers received a capsule containing amphetamine tablets (0.3 mg/kg) on three separate occasions approximately every other day (mean +/- SD, 2.25 +/- 1.13 d apart) in the same environment (scanner suite). At least 2 weeks later, the amphetamine was switched to a placebo of identical appearance and given in the same environmental context. [11C]Raclopride binding to dopamine D(2/3) receptors was assessed after exposure to the first amphetamine-containing pill, after placebo administration, and during a control (no pill) scan. Relative to the control scan, amphetamine administration decreased [11C]raclopride binding potential by 22% in the ventral striatum and 11% in the putamen. Placebo also decreased [11C]raclopride binding potential in the ventral striatum and did so with the same amplitude as amphetamine (23%). These results suggest that cues associated with amphetamine increase dopamine transmission, providing evidence that this system is involved in reward prediction in humans.
authors.affiliation: McConnell Brain Imaging Center, Montreal Neurological Institute, Montreal, Quebec, Canada H3A 2B4. isabelle_boileau@camh.net
authors.forename: Isabelle
authors.initials: I
authors.lastname: Boileau
authors.forename: Alain
authors.initials: A
authors.lastname: Dagher
authors.forename: Marco
authors.initials: M
authors.lastname: Leyton
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Welfeld
authors.forename: Linda
authors.initials: L
authors.lastname: Booij
authors.forename: Mirko
authors.initials: M
authors.lastname: Diksic
authors.forename: Chawki
authors.initials: C
authors.lastname: Benkelfat
mesh_terms: D000328:Adult; D000661:Amphetamine / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D003213:Conditioning, Psychological / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D020891:Raclopride / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism
chemical_list: D002250:Carbon Radioisotopes; D011954:Receptors, Dopamine; D020891:Raclopride; D000661:Amphetamine; D004298:Dopamine