Chronic exposure to a gambling-like schedule of reward predictive stimuli can promote sensitization to amphetamine in rats
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Addiction is considered to be a brain disease caused by chronic exposure to drugs. Sensitization of brain dopamine (DA) systems partly mediates this effect. Pathological gambling (PG) is considered to be a behavioral addiction. Therefore, PG may be caused by chronic exposure to gambling. Identifying a gambling-induced sensitization of DA systems would support this possibility. Gambling rewards evoke DA release. One episode of slot machine play shifts the DA response from reward delivery to onset of cues (spinning reels) for reward, in line with temporal difference learning principles. Thus, conditioned stimuli (CS) play a key role in DA responses to gambling. In primates, DA response to a CS is strongest when reward probability is 50%. Under this schedule the CS elicits an expectancy of reward but provides no information about whether it will occur on a given trial. During gambling, a 50% schedule should elicit maximal DA release. This closely matches reward frequency (46%) on a commercial slot machine. DA release can contribute to sensitization, especially for amphetamine. Chronic exposure to a CS that predicts reward 50% of the time could mimic this effect. We tested this hypothesis in three studies with rats. Animals received 15 × 45-min exposures to a CS that predicted reward with a probability of 0, 25, 50, 75, or 100%. The CS was a light; the reward was a 10% sucrose solution. After training, rats received a sensitizing regimen of five separate doses (1 mg/kg) of d-amphetamine. Lastly they received a 0.5 or 1 mg/kg amphetamine challenge prior to a 90-min locomotor activity test. In all three studies the 50% group displayed greater activity than the other groups in response to both challenge doses. Effect sizes were modest but consistent, as reflected by a significant group × rank association (ϕ = 0.986, p = 0.025). Chronic exposure to a gambling-like schedule of reward predictive stimuli can promote sensitization to amphetamine much like exposure to amphetamine itself.
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There is direct evidence for cross-sensitization of the dopaminergic system under gambling-like conditions in animals.
“There is also direct evidence for cross-sensitization of the dopaminergic system under gambling-like conditions in animals (Mascia et al., 2018; Singer et al., 2012; Zack et al., 2014; Zeeb et al., 2017).”
From Cued for Risk: Evidence for an Incentive Sensitization Framework to Explain the Interplay between Stress and Anxiety, Substance Abuse, and Reward Uncertainty in Disordered Gambling Behavior (2019) · cites this paper as Zack et al., 2014
Rats exposed to maximally uncertain conditions showed the greatest locomotor response to an amphetamine challenge.
“Zack and colleagues found that rats exposed to maximally uncertain conditions showed the greatest locomotor response to an amphetamine challenge (Zack et al., 2014).”
From Cued for Risk: Evidence for an Incentive Sensitization Framework to Explain the Interplay between Stress and Anxiety, Substance Abuse, and Reward Uncertainty in Disordered Gambling Behavior (2019) · cites this paper as Zack et al., 2014
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“dopaminergic system under gambling-like conditions in animals (Mascia et al., 2018; Singer et al., 2012; Zack et al., 2014; Zeeb et al., 2017).”
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- Authors
- Zack, M., Featherstone, R. E., Mathewson, S., & Fletcher, P. J.
- Affiliations
- Centre for Addiction and Mental Health (CA)
- University of Pennsylvania (US)
- Corresponding author
- Zack, Martin
- Venue
- Frontiers in Behavioral Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2014
- Volume
- 8
- Pages
- 36-36
- ISSN
- 1662-5153 (ISSN-L)
- PMC
- PMC3920462
- OpenAlex
- W2010423218
- Cited by
- 108
- References
- 56
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 5 · 2022: 6 · 2021: 4 · 2020: 50 · 2019: 5 · 2018: 7 · 2017: 4 · 2016: 6 · 2015: 7 · 2014: 7
- FWCI
- 3.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Behavioral Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Clinical Psychology › Gambling Behavior and Treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- gambling addiction, amphetamine sensitization, dopamine release, conditioned stimulus, reward probability, temporal difference learning, locomotor activity, drug addiction, behavioral addiction, sucrose reward
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