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Nucleus accumbens corticotropin-releasing factor increases cue-triggered motivation for sucrose reward: paradoxical positive incentive effects in stress?
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Background: Corticotropin-releasing factor (CRF) is typically considered to mediate aversive aspects of stress, fear and anxiety. However, CRF release in the brain is also elicited by natural rewards and incentive cues, raising the possibility that some CRF systems in the brain mediate an independent function of positive incentive motivation, such as amplifying incentive salience. Here we asked whether activation of a limbic CRF subsystem magnifies the increase in positive motivation for reward elicited by incentive cues previously associated with that reward, in a way that might exacerbate cue-triggered binge pursuit of food or other incentives? We assessed the impact of CRF microinjections into the medial shell of nucleus accumbens using a pure incentive version of Pavlovian-Instrumental transfer, a measure specifically sensitive to the incentive salience of reward cues (which it separates from influences of aversive stress, stress reduction, frustration and other traditional explanations for stress-increased behavior). Rats were first trained to press one of two levers to obtain sucrose pellets, and then separately conditioned to associate a Pavlovian cue with free sucrose pellets. On test days, rats received microinjections of vehicle, CRF (250 or 500 ng/0.2 μl) or amphetamine (20 μg/0.2 μl). Lever pressing was assessed in the presence or absence of the Pavlovian cues during a half-hour test. Results: Microinjections of the highest dose of CRF (500 ng) or amphetamine (20 μg) selectively enhanced the ability of Pavlovian reward cues to trigger phasic peaks of increased instrumental performance for a sucrose reward, each peak lasting a minute or so before decaying after the cue. Lever pressing was not enhanced by CRF microinjections in the baseline absence of the Pavlovian cue or during the presentation without a cue, showing that the CRF enhancement could not be explained as a result of generalized motor arousal, frustration or stress, or by persistent attempts to ameliorate aversive states. Conclusion: We conclude that CRF in nucleus accumbens shell amplifies positive motivation for cued rewards, in particular by magnifying incentive salience that is attributed to Pavlovian cues previously associated with those rewards. CRF-induced magnification of incentive salience provides a novel explanation as to why stress may produce cue-triggered bursts of binge eating, drug addiction relapse, or other excessive pursuits of rewards.
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“At the same time, it increases the sensitivity of the excitatory dopaminergic pathway (Peciña et al., 2006).”
From A motivation model of sex addiction – Relevance to the controversy over the concept (2022) · cites this paper as Peciña et al., 2006
Experimental — accuracy not yet measuredIn the citing paper
“CRF in the NAC shell can also enhance the positive motivational value and salience of incentive cues (Pecina et al 2006; Kreibich et al 2009).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Pecina et al 2006
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“In turn, administration of CRF, has been shown to elevate the value of Pavlovian associated reward cues (Peciña et al., 2006).”
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 Peciña et al., 2006
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“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 Pecina et al., 2006
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“For instance, Peciña et al. (2006) trained rats that a CS+ signalled sucrose and a CS− nothing, and then that they could obtain sucrose by pressing one of two levers (R1 → O, R2 → nothing).”
Hoang, I. B., Munier, J. J., Verghese, A., Taira, M., Abiero, A., Leake, J., Dawson, A., Wilcher, M. V. B., Ganesan, K., Ortega, M. E., et al. (2026) · Neuron · doi:10.1016/j.neuron.2026.05.008
Born, M., Krasniqi, S., Riemerschmid, C., Chen, H., Thill, L., Smolka, M. N., Schlagenhauf, F., Heinz, A., Friedel, E., Ebrahimi, C., et al. (2026) · medRxiv · doi:10.64898/2026.09.01.26361915
Stress reduces loss aversion without increasing reward-cue attentional salience
Tommaso, M. D., Coelli, S., Reali, P., Bianchi, A. M., & Actis-Grosso, R. (2026) · Motivation and Emotion · doi:10.1007/s11031-026-10286-7
Metadata
- Authors
- Peciña, S., Schulkin, J., & Berridge, K. C.
- Affiliations
- University of Michigan (US)
- Georgetown University (US)
- Corresponding author
- Peciña, Susana
- Venue
- BMC Biology
- Published
- 2006-04-13
- Volume
- 4
- Issue
- 1
- Pages
- 8-8
- ISSN
- 1741-7007 (ISSN-L)
- PMC
- PMC1459217
- OpenAlex
- W1789705209
- Cited by
- 194
- References
- 64
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 8 · 2023: 5 · 2022: 13 · 2021: 8 · 2020: 5 · 2019: 12 · 2018: 14 · 2017: 6 · 2016: 7 · 2015: 8 · 2014: 14 · 2013: 9 · 2012: 17
- FWCI
- 4.18
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- National Institute of Mental Health (MH-63649, R01MH063649)
- National Institute on Drug Abuse (DA015188, R01DA015188)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- corticotropin-releasing factor, nucleus accumbens shell, incentive salience, Pavlovian-to-instrumental transfer, sucrose reward, incentive motivation, stress, binge eating, amphetamine, reward cues
- MeSH terms
- Animals, Corticotropin-Releasing Hormone, Cues, Male, Microinjections, Motivation, Nucleus Accumbens, Reinforcement, Psychology, Reward, Stress, Physiological, Sucrose, Rats, Sprague-Dawley, Rats
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