Cholecystokinin knock-down in the basolateral amygdala has anxiolytic and antidepressant-like effects in mice
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Cholecystokinin (CCK) is a neuropeptide widely distributed in the mammalian brain. This peptide regulates many physiological functions and behaviors, such as cardio-respiratory control, thermoregulation, nociception, feeding, memory processes and motivational responses, and plays a prominent role in emotional responses including anxiety and depression. CCK-expressing brain regions involved in these functions remain unclear and their identification represents an important step towards understanding CCK function in the brain. The basolateral amygdala (BLA) is strongly involved in emotional processing and expresses high levels of CCK. In this study we examined the contribution of CCK expressed in this brain region to emotional responses in mice. To knockdown CCK specifically in the BLA, we used stereotaxic delivery of recombinant adeno-associated viral vectors expressing a CCK-targeted shRNA. This procedure efficiently reduced CCK levels locally. shCCK-treated animals showed reduced levels of anxiety in the elevated plus-maze, and lower despair-like behavior in the forced swim test. Our data demonstrate that CCK expressed in the BLA represents a key brain substrate for anxiogenic and depressant effects of the peptide. The study also suggests that elevated amygdalar CCK could contribute to panic and major depressive disorders that have been associated with CCK dysfunction in humans.
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Both human and rodents studies indicate a positive correlation of CCK levels and increased anxiety-like behavior.
“Both human and rodents studies indicate a positive correlation of CCK levels and increased anxiety-like behavior [273-275].”
From Anxiety, depression, and the microbiome: A role for gut peptides (2018) · cites this paper as [273]
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Lee, S., Miller, C. L., Bentley, A. R., Brown, M. R., Nagarajan, P., Noordam, R., Morrison, J., Schwander, K., Westerman, K. E., Kho, M., et al. (2025) · Research Square · doi:10.21203/rs.3.rs-6025759/v1
Nakajima, S., Tsuchimine, S., Hira, T., & Kunugi, H. (2025) · Journal of Nutritional Science and Vitaminology · doi:10.3177/jnsv.71.411
Metabolic Roles of Acyl Coenzyme A-Binding Protein (ACBP)/Diazepam Binding Inhibitor (DBI)
Joseph, A. (2021) · theses.fr (ABES) · doi:10.70675/b045685ezd444z4b46zb0f9z0e726ceac466
mGluR5 in EC CCK to BLA Circuit Modulates Depressive‐Like Phenotypes through CCK Signaling
Asim, M., Wang, H., Qianqian, G., Waris, A., & He, J. (2026) · Advanced Science · doi:10.1002/advs.202523115
Караваева, Т. А., Barinov, A. N., Егоров, И. В., Ebzeeva, E. Y., & Ищенко, К. А. (2026) · S S Korsakov Journal of Neurology and Psychiatry · doi:10.17116/jnevro202612607151
Sleep-dependent DNA methylation remodeling in basolateral amygdala fear engrams
Chen, X., Ruan, F., Rodriguez, A. M., Pan, R., Wang, R., Jin, M., 周连艳, Yi, K., Liu, H., Zhou, W., et al. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.118190
- Authors
- Del Boca, C., Lutz, P. E., Le Merrer, J., Koebel, P., & Kieffer, B. L.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Kieffer, B.L.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2012-08
- Volume
- 218
- Pages
- 185-195
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC3532740
- OpenAlex
- W2094060127
- Cited by
- 59
- References
- 54
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 5 · 2023: 4 · 2022: 6 · 2021: 5 · 2020: 7 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 4 · 2015: 2 · 2014: 3 · 2013: 4
- FWCI
- 1.19
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- HAL (submittedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (AA-16658)
- European Commission (GENADDICT/FP6 005166)
- National Institutes of Health
- Institut National de la Santé et de la Recherche Médicale
- Université de Strasbourg
- Centre National de la Recherche Scientifique
- National Institute on Drug Abuse (DA-16768)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- cholecystokinin, basolateral amygdala, anxiety, depression, anxiolytic effects, antidepressant-like effects, shRNA knockdown, adeno-associated virus vectors, emotional processing, despair-like behavior, panic disorder, major depressive disorder
- MeSH terms
- Amygdala, Animals, Anxiety, Cholecystokinin, Depression, Image Processing, Computer-Assisted, Male, Mice, Inbred C57BL, In Situ Hybridization, Reverse Transcriptase Polymerase Chain Reaction, Mice, Gene Knockdown Techniques
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