Expectation Enhances the Regional Brain Metabolic and the Reinforcing Effects of Stimulants in Cocaine Abusers
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The reinforcing effects of drugs of abuse result from the complex interaction between pharmacological effects and conditioned responses. Here we evaluate how expectation affects the response to the stimulant drug methylphenidate in 25 cocaine abusers. The effects of methylphenidate (0.5 mg/kg, i.v.) on brain glucose metabolism (measured by [18 F]deoxyglucose-positron emission tomography) and on its reinforcing effects (self-reports of drug effects) were evaluated in four conditions: (1) expecting placebo and receiving placebo; (2) expecting placebo and receiving methylphenidate; (3) expecting methylphenidate and receiving methylphenidate; (4) expecting methylphenidate and receiving placebo. Methylphenidate increased brain glucose metabolism, and the largest changes were in cerebellum, occipital cortex, and thalamus. The increases in metabolism were ∼50% larger when methylphenidate was expected than when it was not, and these differences were significant in cerebellum (vermis) and thalamus. In contrast, unexpected methylphenidate induced greater increases in left lateral orbitofrontal cortex than when it was expected. Methylphenidate-induced increases in self-reports of “high” were also ∼50% greater when subjects expected to receive it than when they did not and were significantly correlated with the metabolic increases in thalamus but not in cerebellum. These findings provide evidence that expectation amplifies the effects of methylphenidate in brain and its reinforcing effects. They also suggest that the thalamus, a region involved with conditioned responses, may mediate the enhancement of the reinforcing effects of methylphenidate by expectation and that the orbitofrontal cortex mediates the response to unexpected reinforcement. The enhanced cerebellar activation with expectation may reflect conditioned responses that are not linked to conscious responses.
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The firing of DA cells that accompanies drug use encodes reward expectancy, reward learning, and consolidation of contextual memories.
“The firing of DA cells that accompanies drug use encodes a number of reward properties, including reward expectancy [117], reward learning [118], and the consolidation of contextual memories [119].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [117]
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- Authors
- Volkow, N. D., Wang, G.-J., Ma, Y., Fowler, J. S., Zhu, W., Maynard, L., Telang, F., Vaska, P., Ding, Y.-S., Wong, C., & Swanson, J. M.
- Affiliations
- State University of New York (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2003-12-10
- Volume
- 23
- Issue
- 36
- Pages
- 11461-11468
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6740524
- OpenAlex
- W1498104517
- Cited by
- 302
- References
- 48
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 12 · 2022: 9 · 2021: 6 · 2020: 5 · 2019: 14 · 2018: 8 · 2017: 11 · 2016: 20 · 2015: 12 · 2014: 22 · 2013: 20 · 2012: 14
- FWCI
- 4.75
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Energy
- National Institute on Drug Abuse (DA 00280, K20DA000280, DA7092-01)
- Biological and Environmental 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
- expectations, cocaine abusers, methylphenidate, drug reinforcement, conditioned response, brain glucose metabolism, thalamus, cerebellum, orbitofrontal cortex, stimulants
- MeSH terms
- Adult, Central Nervous System Stimulants, Brain, Conditioning, Psychological, Female, Glucose, Humans, Male, Methylphenidate, Reinforcement, Psychology, Tomography, Emission-Computed, Cocaine-Related Disorders
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