Effect of dexmedetomidine on long-term anxiety state after sevoflurane anesthesia in neonatal rats: the role of different central subtypes of α2 receptors

Abstract

Objective To evaluate the effect of dexmedetomidine on the long-term anxiety state after sevoflurane anesthesia in neonatal rats and the role of different central subtypes of α2 receptors. Methods A total of 216 clean-grade healthy male Sprague-Dawley rats, aged 4-6 days, weighing 8-15 g, were divided into 6 groups (n=36 each) using a random number table method: control group (group C), sevoflurane group (group S), dexmedetomidine + sevoflurane group (group D+ S), dexmedetomidine + α2 receptor antagonist atipamezole + sevoflurane group (group D+ A+ S), dexmedetomidine + α2A receptor antagonist BRL44408 + sevoflurane group (group D+ B+ S), and dexmedetomidine + α2C receptor antagonist JP1302 + sevoflurane group (group D+ J+ S). Anesthesia was induced by inhaling 6% sevoflurane for 3 min and maintained by inhaling 2.1% sevoflurane for 6 h. At 30 min before anesthesia induction, dexmedetomidine 25 μg/kg was intraperitoneally injected in group D+ S, dexmedetomidine 25 μg/kg and atipamezole 250 μg/kg were intraperitoneally injected in group D+ A+ S, dexmedetomidine and α2A receptor antagonist BRL44408 1.5 mg/kg were intraperitoneally injected in group D+ B+ S, and dexmedetomidine 25 μg/kg and α2C receptor antagonist JP1302 3 mg/kg were intraperitoneally injected in group D+ J+ S.Twelve rats in each group were randomly selected and sacrificed after the end of anesthesia, blood samples were collected for blood gas analysis, and the serum corticosterone concentration was measured by enzyme-linked immunosorbent assay.The elevated plus maze was performed when the left rats in each group were 60 days old, and 12 rats were selected when the they were 80 days old to perform the restraint stress test. Results Compared with group C, the percentage of time of staying at the open arm was significantly decreased, the total motion distance was shortened, and the serum corticosterone concentration was increased after the end of anesthesia and during the restraint stress test in S, D+ A+ S and D+ B+ S groups (P 0.05). Compared with group S, the percentage of time of staying at the open arm was significantly increased, the total motion distance was prolonged, and the serum corticosterone concentration was decreased after the end of anesthesia and during the restraint stress test in group D+ S and group D+ J+ S (P 0.05). Compared with group D+ S, the percentage of time of staying at the open arm was significantly decreased, the total motion distance was shortened, and the serum corticosterone concentration was increased after the end of anesthesia and during the restraint stress test in D+ A+ S and D+ B+ S groups (P 0.05). Conclusion Dexmedetomidine can reduce the long-term anxiety state after sevoflurane anesthesia in neonatal rats, and the mechanism may be related to activating central α2A receptors and improving hypothalamic-pituitary-adrenocortical axis hyperfunction. Key words: Dexmedetomidine; Anxiety; Anesthetics, inhalation; Infant, newborn; Adolescent; Receptors, adrenergic, alpha-2