title: Rats exposed to isoflurane in utero during early gestation are behaviorally abnormal as adults.
abstract: BACKGROUND
  Preclinical evidence suggests that commonly used anesthetic agents induce long-lasting neurobehavioral changes when administered early in life, but there has been virtually no attention to the neurodevelopmental consequences for the fetus of maternal anesthesia. This study tested the hypothesis that fetal rats exposed to isoflurane during maternal anesthesia on gestational day 14, which corresponds to the second trimester in humans, would be behaviorally abnormal as adults.
  
  
  METHODS
  Timed, pregnant rats were randomly assigned on gestational day 14 to receive 1.4% isoflurane in 100% oxygen (n = 3) or 100% oxygen (n = 2) for 4 h. Beginning at 8 weeks of age, male offspring (N = 12-14 in control and anesthesia groups, respectively) were evaluated for spontaneous locomotor activity, hippocampal-dependent learning and memory (i.e., spontaneous alternations, novel object recognition, and radial arm maze), and anxiety (elevated plus maze).
  
  
  RESULTS
  Isoflurane anesthesia was physiologically well tolerated by the dams. Adult rats exposed prenatally to isoflurane were not different than controls on spontaneous locomotor activity, spontaneous alternations, or object recognition memory, but made more open arm entries on the elevated plus maze and took longer and made more errors of omission on the radial arm maze.
  
  
  CONCLUSIONS
  Rats exposed to isoflurane in utero at a time that corresponds to the second trimester in humans have impaired spatial memory acquisition and reduced anxiety, compared with controls. This suggests the fetal brain may be adversely affected by maternal anesthesia, and raises the possibility that vulnerability to deleterious neurodevelopmental effects of isoflurane begins much earlier in life than previously recognized.
authors.affiliation: Department of Anesthesia, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Arvind
authors.initials: A
authors.lastname: Palanisamy
authors.forename: Mark G
authors.initials: MG
authors.lastname: Baxter
authors.forename: Pamela K
authors.initials: PK
authors.lastname: Keel
authors.forename: Zhongcong
authors.initials: Z
authors.lastname: Xie
authors.forename: Gregory
authors.initials: G
authors.lastname: Crosby
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Culley
mesh_terms: D000758:Anesthesia; D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D001007:Anxiety / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000473:pathology; D005260:Female; D007530:Isoflurane / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D018685:Anesthetics, Inhalation; D005680:gamma-Aminobutyric Acid; D007530:Isoflurane