Melatonin Attenuates Isoflurane-Induced Acute Memory Impairments in Aged Rats

Abstract

Melatonin is an endogenous hormone with neuroprotective effects. Melatonin levels in elderly patients are reduced after surgeries that require anaesthesia. Whether reduced melatonin levels are important for postoperative cognitive dysfunction (POCD) remains unclear. Here, we investigated the effects of melatonin on cognitive dysfunctions induced by isoflurane and mechanisms underlying these effects. Seventy-two 20-month-old Sprague-Dawley rats were randomly divided into six groups (n=12). These groups included M1 and M10 groups that received intraperitoneal melatonin at 1mg/kg or 10mg/kg, respectively, and an ISO group that received 4hr of inhaled 2% isoflurane. They also included M1+ISO and M10+ISO groups that received 1mg/kg or 10mg/kg of melatonin plus 4hr of inhaled 2% isoflurane, respectively, and a control group that received an equal volume of saline. Injections were administered daily for 14 consecutive days. Memory was assessed in the Morris water maze. Plasma and hippocampi were harvested to determine melatonin concentrations and MT1/MT2 receptor expression. Rats treated only with isoflurane showed significantly longer latencies in Morris water maze test trials compared with the control group, with shorter time in the probe trial (p<0.05). Although plasma melatonin levels and MT2 expression in the hippocampus were significantly decreased, MT1 expression was higher in the isoflurane group than in the control group (p<0.001). However, these parameters did not significantly vary in animals administered melatonin compared with controls. Isoflurane may induce cognitive dysfunction by influencing melatonin and MT1/MT2 levels. Melatonin can improve cognitive dysfunction by normalizing plasma melatonin and its receptor levels.