Abstract: Object To investigate the effect of somatostatin receptor subtype-4 agonist(NNC 26-9100) on learning and memory impairment in aged rats induced by isoflurane anesthesia. Methods 20-month-old Sprague Dawley rats were randomly divided into 4 groups(n=14) as follows: V+O2, V+ISO, NNC+ISO and NNC+O2. The NNC+ISO and NNC+O2 groups received bilateral intracerebroventricular injection of NNC 26-9100. The V+O2 and V+ISO groups received equal volume of vehicle control. 24 hours after injection, V+ISO group and NNC+ISO group inhaled 2% isoflurane for 4 hr, while the rest group received 4 hr of 100% O2. Memory was assessed in the Morris water maze. The expression levels of neprilysin(NEP) and insulin degrading enzyme(IDE) in hippocampus were measured by real-time PCR and western blotting. Results Compared with V+ISO group, rats in NNC+ISO group took less time to find platform in day 2 and 3 (P<0.05), spent more time in the target quadrant and crossed more number of platform(P<0.05). There was no significant difference in expression level of NEP and IDE in each group. Conclusion Somatostatin Receptor Subtype-4 Agonist(NNC 26-9100) can improve isoflurane-induced learning and memory dysfunction.

Key words: somatostatin receptor agonist, isoflurane, learning and memory, amyloid β-protein