Transition to drug addiction: a negative reinforcement model based on an allostatic decrease in reward function
Abstract
Rationale The transition from initial drug use to drug addiction has been proposed to result from an allostatic decrease in reward function driven by an overactivation of brain antireward processes. Objectives How decreased reward function explains compulsive drug use is not entirely clear at present, and is still a subject for debate. Methods We present a quantitative model of cocaine self-administration that integrates pharmacokinetic, pharmacodynamic, and motivational factors to address this question. The model assumes that reward system responsivity is a homeostatically regulated process where the desired level of responsivity (called the reward set point) is initially different from the baseline level. The reduction or correction of this difference or error in reward function would drive cocaine self-administration. Results Theoretical data obtained by computer simulation fit the experimental data obtained in animals self-administering cocaine (i.e., the within-session pattern of self-injections, the shape and curvature of the dose-injection function, the nonlinear relationship between drug intake and regulated drug effects). Importantly, simulation of an allostatic decrease in reward system responsivity exacerbates the initial error that drives self-administration, thereby increasing both the intake of, and the motivation for, the drug. This allostatic change manifests as a vertical shift in the dose-injection function similar to that seen in animals with escalating cocaine self-administration. Conclusions The present model provides a satisfactory explanation of escalated drug intake and suggests a novel negative reinforcement view of addiction based on an allostatic decrease in reward function.
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In terms of motivation for drug seeking, a new source of acquired motivation is generated, termed negative reinforcement.
“In terms of the motivation for drug seeking, a new source of acquired motivation is generated, termed negative reinforcement (Ahmed and Koob, 2005).”
From Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development (2021) · cites this paper as Ahmed and Koob, 2005
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- Authors
- Ahmed, S. H., & Koob, G. F.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Scripps Research Institute (US)
- Corresponding author
- Ahmed, Serge H.
- Venue
- Psychopharmacology
- Published
- 2005-02-25
- Volume
- 180
- Issue
- 3
- Pages
- 473-490
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2152911335
- Cited by
- 254
- References
- 8
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 7 · 2023: 11 · 2022: 6 · 2021: 12 · 2020: 17 · 2019: 10 · 2018: 7 · 2017: 13 · 2016: 7 · 2015: 9 · 2014: 15 · 2013: 13 · 2012: 18
- FWCI
- 6.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Drug Abuse (DA04398, R01DA004398)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- drug addiction, cocaine self-administration, negative reinforcement, compulsive drug use
- MeSH terms
- Adaptation, Physiological, Algorithms, Animals, Cocaine, Computer Simulation, Reinforcement, Psychology, Reward, Self Administration, Neural Networks, Computer, Substance-Related Disorders
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