Isoflurane induces cognitive deficits in the Morris water maze task in rats

Abstract

Postoperative cognitive dysfunction has been reported in young, middle-aged and elderly patients with greater incidence with increasing age. Neurocognitive deficits are associated with anaesthetic exposure in aged rodents but in younger adult animals the findings are inconsistent and in middle-aged animals they are unknown. We aimed to compare the effects of moderate duration isoflurane anaesthesia in 100% oxygen on Morris water maze performance in young adult and middle-aged rats. We hypothesised that isoflurane would have greater effects on learning and memory in middle-aged compared with young rats. Young adult (3 months, n = 25) and middle-aged (12 months, n = 20) male Sprague Dawley rats were assigned randomly to isoflurane exposure (1 minimum alveolar concentration, 4 h) or control conditions. Spatial learning (acquisition phase) and memory (probe trial) were tested in the Morris water maze 1 week after exposure. Middle-aged rats were retested in the probe trial 4 weeks after exposure for long-term memory retention. Latency to locate the hidden platform and time spent in the platform quadrant were compared between ages and treatments. Isoflurane did not affect acquisition of the water maze task in either age group. Isoflurane exposure induced a significant deficit in memory retention in young rats, but not middle-aged rats, in the probe trial 24 h after acquisition. Irrespective of treatment, middle-aged rats took longer to acquire the task than young rats. Four weeks after exposure, isoflurane-treated middle-aged rats showed no preference for target location, compared with sham-exposed rats which retained memory for previous platform location. Isoflurane exposure impaired retention memory for platform location 1 week after exposure in young adult rats and resulted in a delayed although weak impairment at 4 weeks in middle-aged rats. The great variation in reported effects of isoflurane suggests a complex effect of this agent on memory which warrants further investigation.