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Updated: Jan 26, 2026

Eye Movement Monitoring of Memory
Published on: August 15, 2010
Disruption of Rapid Eye Movement Sleep Homeostasis in Adolescent Rats after Neonatal Anesthesia
Nadia Lunardi1, Ryan Sica, Navya Atluri
1From the Department of Anesthesiology (N.L., N.A., C.K., Z.Z.) Department of Neurology (H.P.G.), University of Virginia Health System, Charlottesville, Virginia School of Medicine (R.S.) Department of Pharmacology and Neuroscience Graduate Program (K.A.S.) Department of Pharmacology (M.P.B.), University of Virginia, Charlottesville, Virginia.
Insights
Neonatal anesthesia with midazolam, nitrous oxide, and isoflurane significantly increases rapid eye movement (REM) sleep in adolescent rats. These REM sleep alterations persist for at least three weeks post-anesthesia.
Area of Science:
- Neuroscience
- Anesthesiology
- Sleep Medicine
Background:
- Previous studies indicate short-term REM sleep changes after anesthesia in adult rats.
- Long-term effects of neonatal anesthesia on REM sleep architecture remain unclear.
- This study investigates persistent REM sleep alterations following early-life anesthesia.
Purpose of the Study:
- To determine if anesthesia in neonatal rats affects REM sleep during adolescence.
- To test the hypothesis of persistent REM sleep disturbances after early-life anesthesia.
Main Methods:
- Neonatal rats (postnatal day 7) received anesthesia (midazolam, nitrous oxide, isoflurane) or control for 2 or 6 hours.
- EEG and EMG recordings were obtained during adolescence (postnatal days 26-34).
- Primary outcome was total time spent in REM sleep, analyzed via t-tests and ANOVA.
Main Results:
- Anesthesia significantly increased REM sleep duration in adolescent rats compared to controls.
- This increase was observed irrespective of the 2-hour or 6-hour anesthesia duration.
- Specifically, anesthetized rats showed 174.0 ± 7.2 min (2h) and 151.6 ± 9.9 min (6h) of REM sleep versus 108.6 ± 5.3 min and 108.8 ± 7.1 min in controls (P < 0.0001 and P = 0.002, respectively).
Conclusions:
- Neonatal exposure to midazolam, nitrous oxide, and isoflurane leads to increased REM sleep in later life.
- These findings suggest long-lasting effects of early-life anesthesia on sleep regulation.
- Further research is needed to understand the clinical implications of these persistent changes.
Background:
Previous studies suggest that rapid eye movement sleep rebound and disruption of rapid eye movement sleep architecture occur during the first 24 h after general anesthesia with volatile anesthetics in adult rats. However, it is unknown whether rapid eye movement sleep alterations persist beyond the anesthetic recovery phase in neonatal rats. This study tested the hypothesis that rapid eye movement sleep disturbances would be present in adolescent rats treated with anesthesia on postnatal day 7.
Methods:
Forty-four neonatal rats were randomly allocated to treatment with anesthesia consisting of midazolam, nitrous oxide, and isoflurane or control conditions for 2 h or 6 h. Electroencephalographic and electromyographic electrodes were implanted and recordings obtained between postnatal days 26 and 34. The primary outcome was time spent in rapid eye movement sleep. Data were analyzed using two-tailed unpaired t tests and two-way repeated measures analysis of variance.
Results:
Rats treated with midazolam, nitrous oxide, and isoflurane exhibited a significant increase in rapid eye movement sleep three weeks later when compared with control rats, regardless of whether they were treated for 2 h (174.0 ± 7.2 min in anesthetized, 108.6 ± 5.3 in controls, P < 0.0001) or 6 h (151.6 ± 9.9 min in anesthetized, 108.8 ± 7.1 in controls, P = 0.002).
Conclusions:
Treatment with midazolam, nitrous oxide, and isoflurane on postnatal day 7 increases rapid eye movement sleep three weeks later in rats.
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