Conditioned Dopamine Release in Humans: A Positron Emission Tomography [ 11 C]Raclopride Study with Amphetamine
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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.
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Amphetamine increases dopamine release across multiple brain regions in healthy humans, including dorsal and ventral striatum, substantia nigra, and cortex.
“Reductions in ligand binding in PET (130-132, 134, 136, 144-146, 148-154, 157, 159, 161, 162, 164) and SPECT (140, 142, 143, 156) studies in healthy humans indicate that AMP increases DA release across multiple brain regions, including the dorsal and ventral striatum, substantia nigra, and regions of the cortex.”
From The pharmacology of amphetamine and methylphenidate: Relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities (2018) · cites this paper as [130]
The Results section ('Effect of amphetamine and amphetamine-predictive cues on [¹¹C]raclopride BP'; page not available) reports reduced ligand binding after amphetamine in healthy volunteers’ ventral striatum and dorsal putamen, supporting those regions of the claim. The PET acquisition protocol lists the measured regions; it does not report amphetamine-induced dopamine release in the substantia nigra or cortex. The cerebellar cortex was used as a reference region, not reported as a site of increased release. (LLM, conf=0.90)
Experimental — accuracy not yet measuredPET evidence has shown that sensitization to amphetamine in humans leads to carry-over effects in subsequent sessions when placebo is administered.
“Indeed, PET evidence has shown that sensitization to amphetamine in humans leads to carry-over effects in subsequent sessions when placebo is administered (Boileau et al., 2007).”
From A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment (2013) · cites this paper as Boileau et al., 2007
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Self-citation
- Authors
- Boileau, I., Dagher, A., Leyton, M., Welfeld, K., Booij, L., Diksic, M., & Benkelfat, C.
- Affiliations
- Montreal Neurological Institute and Hospital (CA)
- Centre for Addiction and Mental Health (CA)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-04-11
- Volume
- 27
- Issue
- 15
- Pages
- 3998-4003
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6672545
- OpenAlex
- W2046517881
- Cited by
- 222
- References
- 56
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 6 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 69 · 2019: 6 · 2018: 9 · 2017: 10 · 2016: 5 · 2015: 7 · 2014: 17 · 2013: 15 · 2012: 9
- FWCI
- 5.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- amphetamine, [11C]raclopride, dopamine D2/D3 receptors, striatum, ventral striatum, putamen, drug cues, reward prediction, drug craving, relapse, drug-seeking behavior, placebo
- MeSH terms
- Adult, Amphetamine, Carbon Radioisotopes, Conditioning, Psychological, Dopamine, Humans, Male, Protein Binding, Receptors, Dopamine, Raclopride, Positron-Emission Tomography
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