Acute hypoglycemia causes depressive-like behaviors in mice
Open accessAbstract
Reports in humans advocate a link between hypoglycemia and altered mood. Such observations, however, have not been mechanistically explored. Here we examined depressive-like behaviors in mice resulting from acute hypoglycemia. Mice were fasted for 12 hours and then administered intraperitoneal insulin to induce a blood glucose nadir of 50 mg/dL at 0.75 hour after injection that by 2 hours postinjection had returned to normal. The behaviors of locomotion, forced swim, saccharin preference, and novel object recognition were subsequently examined. Mice made hypoglycemic showed depressive-like behaviors 24 hours after resolution of hypoglycemia as evidenced by increased immobility in the forced swim test (FST) and reduced saccharin preference. Movement and memory were not impacted by hypoglycemia 24 hours after its resolution. By 48 hours posthypoglycemia, depressive-like behaviors resolved. In contrast, neither peripheral insulin administration without resultant hypoglycemia nor intracerebroventricular insulin administration altered performance in the FST. The antidepressants fluoxetine and desipramine prevented hypoglycemia-induced immobility in the FST, as did the antiadrenergic agents phentolamine, metoprolol, and butoxamine. Epinephrine and norepinephrine administration caused increased immobility in the FST at 24 hours postadministration that subsequently resolved by 48 hours. These data indicate that, in mice, acute hypoglycemia through adrenergic pathways caused depressive-like behaviors that exist well beyond the resolution of hypoglycemia.
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In an animal model of depression, insulin-induced hypoglycemia lasting less than 2 hours resulted in depressive-like behaviors in mice persisting 24-48 hours.
“In an animal model of depression, insulin-induced hypoglycemia, lasting ,2 h, was shown to result in depressive-like behaviors in mice, which persisted for 24-48 h (41).”
From High glycemic index diet as a risk factor for depression: analyses from the Women’s Health Initiative (2015) · cites this paper as [41]
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- Authors
- Park, M. J., Yoo, S. W., Choe, B. S., Dantzer, R., & Freund, G. G.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- Corresponding author
- Freund, Gregory G.
- Venue
- Metabolism
- Publisher
- Elsevier BV
- Published
- 2012-02
- Volume
- 61
- Issue
- 2
- Pages
- 229-236
- ISSN
- 0026-0495 (ISSN-L)
- PMC
- PMC3245368
- OpenAlex
- W2036433641
- Cited by
- 41
- References
- 44
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 7 · 2020: 3 · 2018: 2 · 2017: 2 · 2015: 3 · 2014: 2 · 2013: 7 · 2012: 1
- FWCI
- 2.34
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (AA019357, RC1AA019357)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK064862, DK 064862)
- National Institute of Neurological Disorders and Stroke (R01NS058525, NS058525)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- hypoglycemia, depression-like behavior, insulin-induced hypoglycemia, forced swim test, saccharin preference, novel object recognition, locomotion, adrenergic pathways, epinephrine, norepinephrine, antidepressants, fluoxetine, desipramine, phentolamine, metoprolol, butoxamine, mood
- MeSH terms
- Acute Disease, Animals, Behavior, Animal, Blood Glucose, Depression, Disease Models, Animal, Epinephrine, Hypoglycemia, Insulin, Male, Mice, Inbred C57BL, Norepinephrine, Stress, Physiological, Swimming, Mice, Infusions, Intraventricular
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