The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Reinforcing Effects of Psychostimulants in Humans Are Associated with Increases in Brain Dopamine and Occupancy of D2Receptors
Abstract
Increases in dopamine concentration in limbic brain regions have been postulated to underlie the reinforcing effects of psychostimulant drugs in laboratory animals. However, neither the qualitative nor the quantitative relationship between drug-induced increases in brain dopamine and the reinforcing effects of psychostimulant drugs have been investigated in humans. Positron emission tomograph and [(11)C]raclopride, a dopamine D(2) receptor radioligand that competes with endogenous dopamine for occupancy of the D(2) receptors, were used to measure changes in brain dopamine after different doses of i.v. methylphenidate in 14 healthy controls. In parallel, measures for self-reports of drug effects were obtained to assess their relationship to methylphenidate-induced changes in brain dopamine. The intensity of the "high" induced by methylphenidate was significantly correlated with the levels of released dopamine (r = 0.78, p <.001); subjects having the greatest increases were those who perceived the most intense high. This relationship remained significant after partialing out for dose and concentration of methylphenidate in plasma. Furthermore, subjects for whom methylphenidate did not increase dopamine did not perceive a high. These results represent the first clear demonstration that stimulant-induced high, a mood descriptor that reflects reinforcing effects of drugs in humans, is associated with increases in brain dopamine, and also that there is a quantitative relationship between levels of D(2) receptor occupancy by dopamine and the intensity of the high.
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Cites
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“, 1993), differences in binding between placebo and MP predominantly reflect MP-induced changes in synaptic DA, which occupies DA D2 receptors (Volkow et al., 1994; Breier et al., 1997).”
Decreased striatal dopaminergic responsiveness in detoxified cocaine-dependent subjects
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Self-citationRelationship between subjective effects of cocaine and dopamine transporter occupancy
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“The D2 radioligand competition method offers a relative estimate of changes in DA concentration, which has been shown to be linearly related to measures of extracellular DA as assessed with microdialysis in nonhuman primate studies (Breier et al., 1997; Laruelle et al., 1997b).”
BackgroundInfluentialProfound neuronal plasticity in response to inactivation of the dopamine transporter
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Cited by
The reward circuit: linking primate anatomy and human imaging
Haber, S. N., & Knutson, B. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.129 · Cited by 3,718
Dopamine, learning and motivation.
Wise, R. A. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1406 · Cited by 3,379
The debate over dopamine’s role in reward: the case for incentive salience
Berridge, K. C. (2007) · Psychopharmacology · doi:10.1007/s00213-006-0578-x · Cited by 2,347
Anticipation of Increasing Monetary Reward Selectively Recruits Nucleus Accumbens
Knutson, B., Adams, C. M., Fong, G. W., & Hommer, D. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-16-j0002.2001 · Cited by 2,244
Inhibition and impulsivity: behavioral and neural basis of response control
Bari, A., & Robbins, T. W. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.06.005 · Cited by 1,921
Metadata
- Authors
- Volkow, N. D., Wang, G.-J., Fowler, J. S., Logan, J., Gatley, S. J., Wong, C., Hitzemann, R., & Pappas, N. R.
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 1999-10
- Volume
- 291
- Issue
- 1
- Pages
- 409-415
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W2240581719
- Cited by
- 422
- References
- 48
- FWCI
- 4.70
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Reinforcing Effects of Psychostimulants in Humans Are Associated with Increases in Brain Dopamine and Occupancy of D2Receptors. https://app.cochat.ai/papers/10.1016/s0022-3565(24)35115-8
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- Volkow, N. D., Wang, G.-J., Fowler, J. S., Logan, J., Gatley, S. J., Wong, C., Hitzemann, R., & Pappas, N. R. (1999). Reinforcing Effects of Psychostimulants in Humans Are Associated with Increases in Brain Dopamine and Occupancy of D2Receptors. The Journal of Pharmacology and Experimental Therapeutics. https://doi.org/10.1016/s0022-3565(24)35115-8
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
