Single and repeated exposures to the volatile anesthetic isoflurane do not impair operant performance in aged rats

• The effects of isoflurane on operant performance in aged rats were assessed.
• Operant tasks measured behavioral inhibition, counting, sequential learning, and motivation.
• Single and repeated exposures to isoflurane did not disrupt performance of aged rats.
• Impairments associated with isoflurane exposure may not generalize to all aspects of cognition.

Postoperative Cognitive Dysfunction (POCD) is a complication that can occur in the elderly after anesthesia and surgery and is characterized by impairments in information processing, memory, and executive function. Currently, it is unclear whether POCD is due to the effects of surgery, anesthesia, or perhaps some interaction between these or other perioperative variables. Studies in rodents suggest that the development of POCD may be related directly to anesthesia-induced neuroactivity. Volatile anesthetics have been shown to increase cellular inflammation and apoptosis within the hippocampus of aged rodents, while producing corresponding impairments in hippocampal-dependent brain functions. However, it is unclear whether volatile anesthetics can affect additional aspects of cognition that do not primarily depend upon the hippocampus. The purpose of this study was to use established operant tests to examine the effects of isoflurane on aspects of behavioral inhibition, learning, and motivation in aged rats. Twenty-one adult Sprague-Dawley rats (11 male, 10 female) were trained to perform fixed consecutive number (FCN), incremental repeated acquisition (IRA), and progressive ratio (PR) tasks for a minimum of 15 months prior to receiving anesthesia. At 23 months of age, rats were exposed to 1.3% isoflurane or medical grade air for 2 h. Initial results revealed that a 2 h exposure to isoflurane had no effect on IRA, FCN, or PR performance. Thus, rats received 3 additional exposures to 1.3% isoflurane or medical grade air: 2, 4 and 6 h exposures with 2 weeks elapsing before exposure two, 3 weeks elapsing between exposures two and three, and 2 weeks elapsing between exposures three and four. These additional exposures had no observable effects on performance of any operant task. These results suggest that single and repeated exposures to isoflurane do not impair the performance of aged rats in tasks designed to measure behavioral inhibition, learning, and motivation. This lack of significant effect suggests that the impairments associated with isoflurane exposure may not generalize to all aspects of cognition, but may be selective to tasks that primarily measure spatial memory processes.