Neuropeptide Y attenuates anxiety- and depression-like effects of cholecystokinin-4 in mice
Abstract
We investigated the involvement of neuropeptide Y (NPY) in the modulation of cholecystokinin-4 (CCK-4)-evoked anxiety and depression. Adult male mice were injected with vehicle, CCK-4, NPY, NPY Y1 receptor agonist [Leu(31), Pro(34)]-NPY or antagonist BIBP3226, via intracerebroventricular route, and subjected to social interaction or forced swim test (FST) for the evaluation of anxiety- and depression-like phenotypes, respectively. To assess the interactions between the two systems, if any, NPYergic agents were administered prior to CCK-4 and the animals were subjected to these behavioral tests. Treatment with CCK-4 or BIBP3226 dose-dependently reduced social interaction time, while NPY or [Leu(31), Pro(34)]-NPY produced opposite effect. CCK-4 treatment increased immobility time in FST. This effect was reversed by NPY and [Leu(31), Pro(34)]-NPY, although BIBP3226 per se did not alter the immobility time. In a combination study, the anxiogenic or depressive effects of CCK-4 were attenuated by NPY or [Leu(31), Pro(34)]-NPY and potentiated by BIBP3226. The brains of CCK-4 treated rats were processed for NPY immunohistochemistry. Following CCK-4 treatment, the nucleus accumbens shell (AcbSh), ventral part of lateral division of the bed nucleus of stria terminalis (BSTLV), hypothalamic paraventricular nucleus and locus coeruleus showed a reduction in NPY-immunoreactive fibers. Population of NPY-immunopositive cells was also decreased in the AcbSh, BSTLV, prefrontal cortex and hypothalamic arcuate nucleus (ARC). However, NPY-immunoreaction in the fibers of the ARC and cells of the central nucleus of amygdala was unchanged. We conclude that, inhibition of NPY signaling in the brain by CCK-4 might be causal to anxiety- and depression-like behaviors.
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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 [275]
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- Authors
- Desai, S. J., Borkar, C. D., Nakhate, K. T., Subhedar, N. K., & Kokare, D. M.
- Affiliations
- Western University (CA)
- Rashtrasant Tukadoji Maharaj Nagpur University (IN)
- Rungta College (IN)
- Indian Institute of Science Education and Research Pune (IN)
- Corresponding author
- Kokare, D.M.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2014-09
- Volume
- 277
- Pages
- 818-830
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2075173107
- Cited by
- 50
- References
- 77
- Citations by year
- 2025: 2 · 2024: 15 · 2023: 4 · 2022: 5 · 2021: 4 · 2020: 4 · 2019: 5 · 2018: 3 · 2017: 1 · 2016: 5 · 2015: 1 · 2014: 1
- FWCI
- 1.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Government of India (BT/PR4909/MED/30/746/2012)
- 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 › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- neuropeptide Y, anxiety-like behavior, depression-like behavior, NPY Y1 receptor, BIBP3226, nucleus accumbens shell, bed nucleus of the stria terminalis, paraventricular nucleus, locus coeruleus, hypothalamic arcuate nucleus, central amygdala, social interaction, forced swim test, neuroendocrine regulation
- MeSH terms
- Animals, Anxiety, Arginine, Brain, Depression, Disease Models, Animal, Dose-Response Relationship, Drug, Immunohistochemistry, Male, Motor Activity, Neuropeptide Y, Neuropsychological Tests, Psychotropic Drugs, Social Behavior, Swimming, Tetragastrin, Anti-Anxiety Agents, Receptors, Neuropeptide Y, Mice
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