Fang Ding1,2, Limin Zheng1, Min Liu3, Rongfa Chen1, L Stan Leung4, Tao Luo5. 1. Department of Anesthesiology, Peking University Shenzhen Hospital, 1120 Lianhua Road, Shenzhen, Guangdong, China. 2. Anhui Medical University, Hefei, Anhui, China. 3. Shenzhen Advanced Medical Education Center, Shenzhen, Guangdong, China. 4. Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada. 5. Department of Anesthesiology, Peking University Shenzhen Hospital, 1120 Lianhua Road, Shenzhen, Guangdong, China. luotao_wh@yahoo.com.
Abstract
BACKGROUND: Exposure to volatile anesthetics has been reported to cause temporary or sustained impairments in learning and memory in pre-clinical studies. The selective antagonists of the histamine H3 receptors (H3R) are considered to be a promising group of novel therapeutic agents for the treatment of cognitive disorders. The aim of this study was to evaluate the effect of H3R antagonist ciproxifan on isoflurane-induced deficits in an object recognition task. METHODS: Adult C57BL/6 J mice were exposed to isoflurane (1.3 %) or vehicle gas for 2 h. The object recognition tests were carried at 24 h or 7 days after exposure to anesthesia to exploit the tendency of mice to prefer exploring novel objects in an environment when a familiar object is also present. During the training phase, two identical objects were placed in two defined sites of the chamber. During the test phase, performed 1 or 24 h after the training phase, one of the objects was replaced by a new object with a different shape. The time spent exploring each object was recorded. RESULTS: A robust deficit in object recognition memory occurred 1 day after exposure to isoflurane anesthesia. Isoflurane-treated mice spent significantly less time exploring a novel object at 1 h but not at 24 h after the training phase. The deficit in short-term memory was reversed by the administration of ciproxifan 30 min before behavioral training. CONCLUSION: Isoflurane exposure induces reversible deficits in object recognition memory. Ciproxifan appears to be a potential therapeutic agent for improving post-anesthesia cognitive memory performance.
BACKGROUND: Exposure to volatile anesthetics has been reported to cause temporary or sustained impairments in learning and memory in pre-clinical studies. The selective antagonists of the histamine H3 receptors (H3R) are considered to be a promising group of novel therapeutic agents for the treatment of cognitive disorders. The aim of this study was to evaluate the effect of H3R antagonist ciproxifan on isoflurane-induced deficits in an object recognition task. METHODS: Adult C57BL/6 J mice were exposed to isoflurane (1.3 %) or vehicle gas for 2 h. The object recognition tests were carried at 24 h or 7 days after exposure to anesthesia to exploit the tendency of mice to prefer exploring novel objects in an environment when a familiar object is also present. During the training phase, two identical objects were placed in two defined sites of the chamber. During the test phase, performed 1 or 24 h after the training phase, one of the objects was replaced by a new object with a different shape. The time spent exploring each object was recorded. RESULTS: A robust deficit in object recognition memory occurred 1 day after exposure to isoflurane anesthesia. Isoflurane-treated mice spent significantly less time exploring a novel object at 1 h but not at 24 h after the training phase. The deficit in short-term memory was reversed by the administration of ciproxifan 30 min before behavioral training. CONCLUSION:Isoflurane exposure induces reversible deficits in object recognition memory. Ciproxifan appears to be a potential therapeutic agent for improving post-anesthesia cognitive memory performance.
Authors: Gerard B Fox; Timothy A Esbenshade; Jia Bao Pan; Richard J Radek; Kathleen M Krueger; Betty B Yao; Kaitlin E Browman; Michael J Buckley; Michael E Ballard; Victoria A Komater; Holly Miner; Min Zhang; Ramin Faghih; Lynne E Rueter; R Scott Bitner; Karla U Drescher; Jill Wetter; Kennan Marsh; Martine Lemaire; Roger D Porsolt; Youssef L Bennani; James P Sullivan; Marlon D Cowart; Michael W Decker; Arthur A Hancock Journal: J Pharmacol Exp Ther Date: 2004-12-17 Impact factor: 4.030