Behavioural sensitization to repeated sleep deprivation in a mice model of mania
Abstract
Sensitization to the effect of stress has been hypothesized as a mechanism to explain episode recurrence and cycle acceleration in bipolar disorder. Naturalistic observations and experimental work in human patients suggested that sleep deprivation can trigger manic episodes of illness. In rats sleep deprivation (SD) with the platform method caused mania-like behaviours thus providing an animal model of mania with face, construct, and predictive validity. In the present study we administered SD or control stress to male CD1 mice following a dose-response protocol based on time of exposure to the experimental conditions (6, 12 or 24 h) and repetition of treatment (three times). SD, but not stress-control conditions, increased motor activity and aggressive behaviours. The behavioural activation followed a dose-response curve based on length of treatment, with non-significant trends after 6h, significant effects after 12 h, and maximal effects after 24 h. Moreover, the behavioural activation followed a time-response curve, with progressive sensitization to the effects of SD, but not of control stress, upon its repetition. This is the first animal model of behavioural sensitization to the effects of a specific stress (sleep deprivation) known to trigger mania in bipolar patients. We expect it to be useful to test the efficacy of antimanic and mood-stabilizer drugs, and to study the neurobiological correlates of manic reactions in order to gain new insight into the pathophysiology of bipolar illness and to identify new targets for treatment.
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Circadian disruption by sleep deprivation can induce a manic-like phenotype in mice (increased aggression and hyperlocomotion), yet these effects are transient and behaviors return to baseline within 24 hours.
“Circadian disruption by sleep deprivation can induce a manic-like phenotype in mice (increased aggression and hyperlocomotion), yet these effects are transient and behaviors return to baseline within 24 h136.”
From Circadian rhythm disruption and mental health (2020) · cites this paper as [136]
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Circadian rhythm disruption and mental health
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- Authors
- BENEDETTI, F., FRESI, F., MACCIONI, P., & SMERALDI, E.
- Affiliations
- Vita-Salute San Raffaele University (IT)
- Corresponding author
- BENEDETTI, F
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2008-03-05
- Volume
- 187
- Issue
- 2
- Pages
- 221-227
- ISSN
- 0166-4328 (ISSN-L)
- OpenAlex
- W1970821619
- Cited by
- 85
- References
- 52
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 4 · 2022: 3 · 2021: 3 · 2020: 5 · 2019: 8 · 2018: 1 · 2017: 5 · 2016: 4 · 2015: 9 · 2014: 10 · 2013: 5 · 2012: 3
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- sleep deprivation, mania, bipolar disorder, behavioral sensitization, stress sensitization, animal model of mania, ICR mice, motor activity, aggression, mood stabilizers, antimanic drugs
- MeSH terms
- Aggression, Analysis of Variance, Animals, Behavior, Animal, Bipolar Disorder, Circadian Rhythm, Disease Models, Animal, Male, Motor Activity, Sensitivity and Specificity, Sleep Deprivation, Stress, Psychological, Time Factors, Reproducibility of Results, Mice
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