Orexin-1 receptor is involved in ageing-related delayed emergence from general anaesthesia in rats.

Abstract

Previous clinical studies have shown that emergence from isoflurane anaesthesia takes longer in elderly patients compared with middle-aged patients. The current study investigated whether delayed emergence from anaesthesia in older age is associated with the age-related decrease in orexin receptors by using a rat model. Adult and aged Sprague-Dawley rats were used to assess the time to emergence after 30 min isoflurane anaesthesia (1.4 vol%), and differences in the orexinergic systems, including the number of orexinergic neurones, plasma orexin concentrations, and expression of orexin-1 (OX1R) and orexin-2 receptors, compared using immunofluorescence, radioimmunoassay, western blot, and real-time polymerase chain reaction. The effects of OX1R expression on emergence time were determined by virus-mediated overexpression of OX1R using intra-cerebroventricular injection. The median (range) emergence time of aged rats was longer than that in adult rats [1082 (1010-1130) compared with 848 (829-938) s; P=0.0009]. Plasma orexin concentrations were higher in the aged group than the adult group [34 (33-37) and 25 (22-31) pg ml^-1, respectively; P=0.04], but the number of orexinergic neurones was similar in both groups. Protein expression of OX1R was lower in the aged group compared with the adult group [0.47 (0.35-0.58) compared with 0.97 (0.86-1.32), respectively; P=0.002]. Overexpression of OX1R significantly shortened the emergence time in aged rats from [1120 (1040-1190) s] to [769 (576-928) s; P=0.03]. Age-related decrease in OX1R expression is associated with delayed emergence from isoflurane anaesthesia in aged rats.