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Incentive Sensitization by Previous Amphetamine Exposure: Increased Cue-Triggered “Wanting” for Sucrose Reward
Open accessAbstract
We reported previously that an amphetamine microinjection into the nucleus accumbens enables Pavlovian reward cues in a conditioned incentive paradigm to trigger excessive instrumental pursuit. Here we show that sensitization caused by previous amphetamine administration also causes reward cues to trigger excessive pursuit of their associated reward, even when sensitized rats are tested in a drug-free state. Rats learned to lever press for sucrose pellets, and they separately learned to associate sucrose pellets with Pavlovian cues (30 sec auditory cues). Amphetamine sensitization was induced by six daily injections of amphetamine (3 mg/kg, i.p.; controls received saline). Rats were tested for lever pressing under extinction conditions 10 d later, after a bilateral microinjection of intra-accumbens vehicle or amphetamine (5 microg/0.5 microl per side). Cue-triggered pursuit of sucrose reward was assessed by increases in pressing on the sucrose-associated lever during intermittent presentations of a free conditioned stimulus (CS+) sucrose cue. Sensitized rats pressed at normal levels during baseline and during the CS-, but the CS+ triggered 100% greater increases in pressing from sensitized rats than from control rats after vehicle microinjection. Sensitization therefore enhanced the incentive salience attributed to the CS+ even when rats were tested while drug-free. For control rats, a microinjection of intra-accumbens amphetamine was needed to produce the same enhancement of cue-triggered reward "wanting." The amphetamine microinjection also interacted synergistically in sensitized rats to produce intrusive cue-triggered pursuit behaviors (e.g., investigatory sniffing) that interfered with goal-directed lever pressing. These results support the incentive-sensitization theory postulate that sensitization causes excessive cue-triggered "wanting" for an associated reward.
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“For example, in animal studies, sensitization increases neuronal firing in VTA–accumbens–pallidal pathways that code incentive salience as well as the behavioral ability of reward cues to trigger frenzied bursts of effort to obtain the reward (Peciña & Berridge, 2013; Tindell et al., 2005; Wyvell & Berridge, 2001).”
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 Wyvell & Berridge, 2001
In the citing paper
“This and related studies (Wyvell and Berridge, 2000; 2001; Pecina et al., 2006) demonstrate that increased activity of intra-shell dopamine does not merely enhance motor-habits, but also enhances motivation for rewards, a finding consistent with the notion of action-arousal or drive.”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Wyvell and Berridge, 2001
In the citing paper
“Wyvell and Berridge (2001) further found that previous experience with repeated administration of amphetamine has essentially the same effect on incentive salience attribution as intra-shell administration of amphetamine.”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Wyvell and Berridge (2001)
In the citing paper
“Interestingly, intra-shell administration of amphetamine in those sensitized rats did not further increase conditioned responding upon the presentation of a conditioned stimulus, but rather increased general investigatory behaviors such as sniffing and rearing not targeted at the active lever (Wyvell and Berridge, 2001).”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Wyvell and Berridge, 2001
In the citing paper
“These effects also appear to be largely dependent on the VS [43–45].”
From Contributions of the striatum to learning, motivation, and performance: an associative account (2012) · cites this paper as [45]
In the citing paper
“amphetamine injection into the Nacc enhances PIT, without affecting base rates of instrumental responding [45].”
From Contributions of the striatum to learning, motivation, and performance: an associative account (2012) · cites this paper as [45]
In the citing paper
“These behavioral phenotypes are accompanied by baseline differences in dopamine transmission, with bHRs showing elevated sensitivity to dopamine agonists, increased proportion of striatal D2receptors in a high-affinity state, greater frequency of spontaneous dopamine transients15, and higher reward-related dopamine release prior to conditioning, all of which could enhance their attribution of in”
From A selective role for dopamine in stimulus-reward learning (2011) · cites this paper as [30]
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Metadata
- Authors
- Wyvell, C. L., & Berridge, K. C.
- Affiliations
- University of Michigan (US)
- ORCID
- Berridge, Kent C.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2001-10-01
- Volume
- 21
- Issue
- 19
- Pages
- 7831-7840
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6762900
- OpenAlex
- W2145827196
- Cited by
- 436
- References
- 66
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 6 · 2023: 11 · 2022: 5 · 2021: 12 · 2020: 52 · 2019: 9 · 2018: 9 · 2017: 11 · 2016: 17 · 2015: 17 · 2014: 17 · 2013: 28 · 2012: 34
- FWCI
- 5.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (9604408)
- National Institute on Drug Abuse (F31 DA0599901)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Social Sciences › Psychology › Clinical Psychology › Gambling Behavior and Treatments
- Keywords
- amphetamine sensitization, incentive salience, nucleus accumbens, instrumental behavior, goal-directed behavior, sucrose reward, incentive-sensitization theory
- MeSH terms
- Acoustic Stimulation, Amphetamine, Animals, Behavior, Animal, Conditioning, Classical, Conditioning, Operant, Cues, Extinction, Psychological, Female, Injections, Intraperitoneal, Microinjections, Motivation, Nucleus Accumbens, Reinforcement, Psychology, Reward, Sucrose, Rats, Sprague-Dawley, Amphetamine-Related Disorders, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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