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The Journal of Neuroscience, April 11, 2007, 27(15):3998-4003; doi:10.1523/JNEUROSCI.4370-06.2007

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Behavioral/Systems/Cognitive
Conditioned Dopamine Release in Humans: A Positron Emission Tomography [¹¹C]Raclopride Study with Amphetamine

Isabelle Boileau,^1,2 Alain Dagher,^1,2 Marco Leyton,^1,2,3 Krzysztof Welfeld,³ Linda Booij,³ Mirko Diksic,¹ and Chawki Benkelfat^1,2,3

¹McConnell Brain Imaging Center, Montreal Neurological Institute, Montreal, Quebec, Canada H3A 2B4, and ²Departments of Neurology and Neurosurgery and ³Psychiatry, McGill University, Montréal, Québec, Canada H3A 1A1

Correspondence should be addressed to Dr. Isabelle Boileau, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada M5T 1R8. Email: isabelle_boileau{at}camh.net

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.

Key words: positron emission tomography; dopamine; amphetamine; conditioning; placebo; addiction

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Received Oct. 6, 2006; revised Feb. 12, 2007; accepted Feb. 28, 2007.

Correspondence should be addressed to Dr. Isabelle Boileau, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada M5T 1R8. Email: isabelle_boileau{at}camh.net

This article has been cited by other articles:

				W. K. Schiffer, C. N. B. Liebling, C. Reiszel, J. M. Hooker, J. D. Brodie, and S. L. Dewey Cue-Induced Dopamine Release Predicts Cocaine Preference: Positron Emission Tomography Studies in Freely Moving Rodents J. Neurosci., May 13, 2009; 29(19): 6176 - 6185. [Abstract] [Full Text] [PDF]

				T. E Robinson and K. C Berridge The incentive sensitization theory of addiction: some current issues Phil Trans R Soc B, October 12, 2008; 363(1507): 3137 - 3146. [Abstract] [Full Text] [PDF]

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