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Multiple Anesthetic Exposure in Infant Monkeys Alters Emotional Reactivity to an Acute Stressor
Jessica Raper1, Maria C Alvarado, Kathy L Murphy
1From the Division of Developmental and Cognitive Neuroscience, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia (J.R., M.C.A.); Department of Experimental Psychology, Oxford University, Oxford, United Kingdom (K.L.M.); and Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York (M.G.B.).
Insights
Repeated exposure to sevoflurane anesthesia in infant rhesus monkeys led to significantly higher anxiety-related behaviors in later life. This suggests potential long-term adverse effects of early-life anesthesia on emotional development.
Area of Science:
- Neuroscience
- Developmental Psychology
- Anesthesiology
Background:
- Human studies indicate a link between early-life anesthesia and learning disabilities.
- Rodent models show postnatal anesthetic exposure causes neurotoxicity and cognitive deficits.
- A rhesus monkey model was used to investigate long-term behavioral changes from repeated postnatal anesthetic exposure.
Purpose of the Study:
- To determine if repeated postnatal anesthetic exposure is sufficient to induce long-term behavioral changes in rhesus monkeys.
- To assess the impact of early-life anesthesia on emotional reactivity in a translationally relevant primate model.
Main Methods:
- Rhesus monkeys (n=20) received either three 4-hour sevoflurane anesthesia exposures or maternal separations on specific postnatal days.
- Monkeys were housed with mothers except for overnight observation periods.
- Emotional reactivity was assessed at 6 months of age using the human intruder paradigm.
Main Results:
- Monkeys exposed to anesthesia as neonates exhibited significantly higher frequencies of anxiety-related behaviors compared to controls (11.04 ± 1.68 vs. 4.79 ± 0.77).
- This difference was observed across all stimulus conditions during the human intruder paradigm test.
Conclusions:
- Increased emotional behavior in infant monkeys following anesthesia exposure suggests potential long-term adverse effects.
- These findings highlight the need for further research into the neurodevelopmental consequences of early-life anesthesia.
Background:
Retrospective studies in humans have shown a higher prevalence of learning disabilities in children that received multiple exposures to general anesthesia before the age of 4 yr. Animal studies, primarily in rodents, have found that postnatal anesthetic exposure causes neurotoxicity and neurocognitive deficits in adulthood. The authors addressed the question of whether repeated postnatal anesthetic exposure was sufficient to cause long-term behavioral changes in a highly translationally relevant rhesus monkey model, allowing study of these variables against a background of protracted nervous system and behavioral development.
Methods:
Rhesus monkeys of both sexes underwent either three 4-h exposures to sevoflurane anesthesia (anesthesia group n = 10) or brief maternal separations (control group n = 10) on postnatal day 6 to 10 that were repeated 14 and 28 days later. Monkeys remained with their mothers in large social groups at all times except for overnight observation after each anesthetic/control procedure. At 6 months of age, each monkey was tested on the human intruder paradigm, a common test for emotional reactivity in nonhuman primates.
Results:
The frequency of anxiety-related behaviors was significantly higher in monkeys that were exposed to anesthesia as neonates as compared with controls: anesthesia 11.04 ± 1.68, controls 4.79 ± 0.77, mean ± SEM across all stimulus conditions.
Conclusion:
Increased emotional behavior in monkeys after anesthesia exposure in infancy may reflect long-term adverse effects of anesthesia.
