Abstract: Objective　To explore the role of the age-related alteration of dopamine D1 receptor in nucleus accumbens (NAc) in the delayed emergence from isoflurane anesthesia in aged mice. Methods　Firstly 8 aged mice (18-22 months) and 8 young mice (5-8 months) were extracted from 26 mice in each group. After exposure to 1.4% isoflurane, differences in the emergence time from isoflurane anesthesia and power spectrum of cortical electroencephalogram (EEG) were compared between the two groups. The rest of the mice in each group were used for microinjection. The effect of microinjecting dopamine D1 receptor agonist, antagonist and normal saline into the NAc on the emergence time and power spectrum were investigated during the recovery period after isoflurane anesthesia. Finally, the differences of expression levels of the NAc dopamine D1 receptor in aged and young mice were detected to analyze the potential mechanism underlying the delayed emergence after general anesthesia in aged mice. Results　Compared with young mice, the emergence time from isoflurane anesthesia was notably prolonged in aged mice (P＜0.01). Power of δ band (＞1-4 Hz) in the cortical EEG was elevated in aged mice (P＜0.01), whilst the power of α band (＞8-12 Hz), β band (＞12-25 Hz) and γ band (＞25-60 Hz) were strikingly reduced (P＜0.05). Comparing with normal saline controls, microinjecting D1 receptor agonist significantly shortened the emergence time, reduced the power of δ band and enhanced the power of γ band in EEG of young mice (P＜0.01). Meanwhile, microinjecting D1 receptor antagonist prolonged the emergence time and increased the power in δ band in young mice (P＜0.01). However, microinjecting D1 receptor agonist/antagonist affected neither the emergence time nor cortical EEG in aged mice (P＞0.05). In addition, the expression level of D1 receptor in the NAc remarkably decreased in aged mice compared with that of young mice (P＜0.01). Conclusion　The age-related downregulation of D1 receptor in the NAc attenuates its arousal-promoting ability for general anesthesia, which is probably a crucial reason for the delayed emergence in aged animals.

Key words: receptors, dopamine, isoflurane, mice, inbred C57BL, electroencephalography, anesthesia, general, delayed emergence, nucleus accumbens