title: Single and repeated exposures to the volatile anesthetic isoflurane do not impair operant performance in aged rats.
abstract: 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 2h. Initial results revealed that a 2h 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 6h 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.
authors: National Center for Toxicological Research (NCTR)/FDA, Division of Neurotoxicology, 3900 NCTR Road, Jefferson, AR 72079, United States. Electronic address: Jennifer.Walters@fda.hhs.gov.
authors: Jennifer L
authors: JL
authors: Walters
authors: National Center for Toxicological Research (NCTR)/FDA, Division of Neurotoxicology, 3900 NCTR Road, Jefferson, AR 72079, United States.
authors: John J
authors: JJ
authors: Chelonis
authors: National Center for Toxicological Research (NCTR)/FDA, Division of Neurotoxicology, 3900 NCTR Road, Jefferson, AR 72079, United States.
authors: Charles M
authors: CM
authors: Fogle
authors: University of Toronto, Department of Physiology, Medical Sciences Building, Room 3318, 1 King⿿s College Circle, Toronto, Ontario M5S1A8, Canada.
authors: Beverley A
authors: BA
authors: Orser
authors: National Center for Toxicological Research (NCTR)/FDA, Division of Neurotoxicology, 3900 NCTR Road, Jefferson, AR 72079, United States.
authors: Merle G
authors: MG
authors: Paule
mesh_terms: D000375:Aging; D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D007530:Isoflurane / Q000633:toxicity*; D007859:Learning Disabilities / Q000139:chemically induced*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018685:Anesthetics, Inhalation; D007530:Isoflurane
keywords: Anesthesia; Fixed consecutive number; Incremental repeated acquisition; Isoflurane; Operant behavior