Multiple sevoflurane exposures in infant monkeys do not impact the mother-infant bond

Abstract

Exposure to general anesthesia during the postnatal period is associated with death of brain cells as well as long-term impairments in cognitive and emotional behavior in animal models. These models are critical for investigating mechanisms of pediatric anesthetic neurotoxicity as well as for testing potential strategies for preventing or mitigating this toxicity. Control conditions for anesthesia exposure involve separation of conscious infants from their mothers for variable periods of time, which could have its own effect on subsequent behavior because of stress to the mother and/or infant as a consequence of separation. We are conducting a long-term study of infant rhesus monkeys exposed three times for 4 hours each to sevoflurane anesthesia during the first six postnatal weeks, with a comparison condition of control infant monkeys that undergo brief maternal separations on the same schedule, to equate the period of time each infant is conscious and separated from its mother. Because mothers are separated from their infants longer for infants in the anesthesia condition, this could modify maternal behavior towards the infant, which may influence subsequent socioemotional behavior in the infants. In this study, we analyzed maternal behavior immediately after the first post-anesthesia (or control) reunion, as well as during reintroduction of the mother-infant pair to the larger social group 24 hours post-anesthesia or control separation, and found no differences between the conditions with mothers spending most of their time in contact with infants in all conditions analyzed. This indicates that the different durations of maternal separation in this study design do not impact the mother-infant bond, strengthening conclusions that subsequent differences in behavior between monkeys exposed to anesthesia compared to controls are a consequence of anesthesia exposure and not differential maternal behavior in the two conditions.

Persistent alteration in behavioural reactivity to a mild social stressor in rhesus monkeys repeatedly exposed to sevoflurane in infancy

“…Thus, on average, control infants experienced 30e40 min of maternal separation and were returned to the dam. Motherinfant interactions after these separations did not differ between groups, 23 indicating that the separations involved in anaesthesia exposures did not cause alterations in motherinfant bonding that might have impacted later cognitive or socio-emotional behaviour.…”

Visual recognition memory is impaired in rhesus monkeys repeatedly exposed to sevoflurane in infancy

“…Thus, on average, control infants experienced 30-40 min of maternal separation and were returned to the dam. Details of the mother-infant interactions after these separations have been published 24 and did not differ between groups, indicating that the separations involved in anaesthesia exposures did not cause alterations in mother-infant bonding that might have impacted later cognitive or socioemotional behavior. Editor's key points…”

Using animal models to evaluate the functional consequences of anesthesia during early neurodevelopment

“…Monkeys were evaluated on the human intruder test, an often-used measure of emotional reactivity in NHPs, when they were 6 months old, and the SEVO-treated monkeys exhibited significantly increased frequency of anxiety-related behaviors compared with the control group. In subsequent work, Raper et al presented evidence suggesting that the observed emotional disturbances in SEVO-treated monkeys were not likely due to differences in mother-infant bonding occurring in the drug and control groups (Raper, Bush, Murphy, Baxter & Alvarado, 2016). No neuropathological findings were reported in these studies.…”

“…There is evidence that developmental ASA exposure induces alterations in emotionality, although concentrated study of this domain is relatively lacking. For example, several rodent and NHP studies have reported alterations in activity [e.g., Fredriksson et al, 2004; 2007 (mouse); Zheng et al, 2013 (rat)]; and anxiety-like behaviors [Man et al, 2015 (mouse); Raper et al, 2016; and Coleman et al, 2017 (monkey)] as a result of neonatal ASA exposure. During the early post-weaning period (P23) we recommend evaluating mice on their reactivity and habituation to handling (Gallitano-Mendel, Wozniak, Pehek, & Milbrandt, 2008).…”