Controversies in translational research: drug self-administration.
Open accessAbstract
Rationale Laboratory animal and human models of drug self-administration are used to evaluate potential pharmacotherapies for drug abuse, yet the utility of these models in predicting clinically useful medications is variable.Objective The objective of this study was to track how antagonist, agonist, and partial agonist medication approaches influence heroin and cocaine self-administration by rodents, non-human primates, and humans and to compare these results to clinical outcomes.Results Across species, heroin self-administration was decreased by all three medication approaches, paralleling their demonstrated clinical utility. The heroin data emphasize the importance of assessing a medication's abuse liability preclinically to predict medication abuse and compliance and of considering subject characteristics (e.g., opioid dependence) when interpreting medication effects. For cocaine, the effects of ecopipam, modafinil, and aripiprazole were consistent in the laboratory and clinic, provided that the medications were administered repeatedly before self-administration sessions. Modafinil attenuated cocaine's reinforcing effects in the human laboratory and improved treatment outcome, while ecopipam and aripiprazole increased the reinforcing effects of cocaine and do not appear promising in the clinic.Conclusions The self-administration model has reliably identified medications to treat opioid dependence, and the recent data with modafinil suggest that the human laboratory model also identifies medications to treat cocaine dependence. There have been numerous false positives when subjective effects are the primary outcome measure, but not when self-administration is the outcome. Factors relevant to the predictive validity of self-administration procedures include medication maintenance and the concurrent assessment of a range of behaviors to determine abuse liability and the specificity of effect.
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Acute compared with chronic antagonism of the dopamine receptor elicits opposite effects on cocaine reinforcement in both human and non-human subjects.
“It has been noted that acute compared with chronic antagonism of the dopamine receptor elicits opposite effects on cocaine reinforcement in both human and non-human subjects 76.”
From Psychosocial and pharmacological interventions for the treatment of cannabis use disorder (2018) · cites this paper as [76]
The Rodents and non-human primates section reports that acute dopamine antagonism can block cocaine reinforcement, while repeated administration can increase it. The Summary and Human laboratory sections report increased cocaine self-administration after chronic ecopipam in humans, but the reported acute human effect is reduced subjective effects and desire for cocaine—not a demonstrated reduction in cocaine reinforcement. (LLM, conf=0.88)
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- Authors
- Haney, M., & Spealman, R.
- Affiliations
- New York State Psychiatric Institute (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Haney, Margaret
- ORCID
- Haney, Margaret
- Venue
- Psychopharmacology
- Published
- 2008-02-19
- Volume
- 199
- Issue
- 3
- Pages
- 403-419
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- PMC
- PMC2731701
- OpenAlex
- W1965528317
- Cited by
- 270
- References
- 187
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 7 · 2023: 5 · 2022: 12 · 2021: 12 · 2020: 16 · 2019: 18 · 2018: 13 · 2017: 17 · 2016: 23 · 2015: 21 · 2014: 15 · 2013: 14 · 2012: 16
- FWCI
- 1.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (DA-09236, DA11054, R01DA019239, DA11928, DA 19239, R01DA017700, R01DA011054, P50DA009236, DA17700, 09236, R01DA011928)
- National Center for Research Resources (RR00 168, K26RR000168, P51RR000168)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Keywords
- self-administration, translational research, heroin addiction, cocaine dependence, opioid antagonists, opioid agonists, partial agonists, modafinil, ecopipam, aripiprazole, abuse liability, predictive validity, non-human primates
- MeSH terms
- Animals, Disease Models, Animal, Heroin Dependence, Humans, Primates, Rodentia, Self Administration, Substance-Related Disorders, Cocaine-Related Disorders
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