Infant isoflurane exposure affects social behaviours, but does not impair specific cognitive domains in juvenile non-human primates

Viola Neudecker, Jose F. Perez-Zoghbi, Kristine Coleman, Martha Neuringer, Nicola Robertson, Alexandra Bemis, Bess Glickman, Katie J. Schenning, Damien A. Fair, Lauren D. Martin, Gregory A. Dissen, Ansgar M. Brambrink

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


BACKGROUND: Clinical studies show that children exposed to anaesthetics for short times at young age perform normally on intelligence tests, but display altered social behaviours. In non-human primates (NHPs), infant anaesthesia exposure for several hours causes neurobehavioural impairments, including delayed motor reflex development and increased anxiety-related behaviours assessed by provoked response testing. However, the effects of anaesthesia on spontaneous social behaviours in juvenile NHPs have not been investigated. We hypothesised that multiple, but not single, 5 h isoflurane exposures in infant NHPs are associated with impairments in specific cognitive domains and altered social behaviours at juvenile age.

METHODS: Eight Rhesus macaques per group were anaesthetised for 5 h using isoflurane one (1×) or three (3×) times between postnatal days 6 and 12 or were exposed to room air (control). Cognitive testing, behavioural assessments in the home environment, and provoked response testing were performed during the first 2 yr of life.

RESULTS: The cognitive functions tested did not differ amongst groups. However, compared to controls, NHPs in the 3× group showed less close social behaviour (P=0.016), and NHPs in the 1× group displayed increased anxiety-related behaviours (P=0.038) and were more inhibited towards novel objects (P<0.001).

CONCLUSIONS: 5 h exposures of NHPs to isoflurane during infancy are associated with decreased close social behaviour after multiple exposures and more anxiety-related behaviours and increased behavioural inhibition after single exposure, but they do not affect the cognitive domains tested. Our findings are consistent with behavioural alterations in social settings reported in clinical studies, which may guide future research.

Original languageEnglish (US)
Pages (from-to)486-499
Number of pages14
JournalBritish Journal of Anaesthesia
Issue number2
StatePublished - Feb 2021
Externally publishedYes

Bibliographical note

Funding Information:
International Anesthesia Research Society (Frontiers in Anesthesia Research Award 2012) to AMB; National Institutes of Health (P51OD011092) to the Oregon National Primate Research Center; International Anesthesia Research Society (Board of Trustees award) to AMB; Departments of Anesthesiology of Oregon Health & Science University and Columbia University to AMB; Emory University, the University of North Carolina, and NOUS Imaging, Inc. to DAF.

Publisher Copyright:
© 2020 British Journal of Anaesthesia


  • anaesthesia
  • behaviour
  • brain development
  • cognitive testing
  • neurotoxicity
  • non-human primate
  • social behaviour
  • Age Factors
  • Male
  • Macaca mulatta
  • Anxiety/chemically induced
  • Brain/drug effects
  • Anesthetics, Inhalation/administration & dosage
  • Time Factors
  • Behavior, Animal/drug effects
  • Social Behavior
  • Reaction Time/drug effects
  • Female
  • Isoflurane/administration & dosage
  • Motor Activity/drug effects
  • Animals, Newborn
  • Exploratory Behavior/drug effects
  • Drug Administration Schedule
  • Neurotoxicity Syndromes/etiology
  • Animals
  • Cognition/drug effects

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Journal Article
  • Research Support, N.I.H., Extramural


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