Effects of Posttraining Administration of Insulin on Retention of a Habituation Response in Mice: Participation of a Central Cholinergic Mechanism |
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| Institution: | 1. Optics and Imaging Centre, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa;2. Women’s Health and HIV Research Group, Department of Obstetrics and Gynaecology, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa;1. Laboratory of Innate Immunity, Canada;2. CHU-Sainte-Justine Research Center, Canada;3. Department of Microbiology, Infectiology & Immunology, Canada;4. Department of Pediatrics, Canada;5. Division of Infectious Diseases, CHUM, Canada;6. University of Montreal, Montreal, Canada;7. Department of Biological Science, UQAM, Montreal, Canada;8. McGill University Health Center, McGill University, Montreal, Canada;1. Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan;2. Department of Surgery, Tohoku University Hospital, Sendai, Japan;1. College of Chemistry and Chemical Engineering, Chongqing University of Technology, 69 Hongguang Rd, Lijiatuo, Banan District, Chongqing 400054, PR China;2. Institute of Microstructure and Properties of Advanced Materials, Beijing University of Technology, Beijing 100124, PR China;3. College of Materials Science and Engineering, Beijing University of Technology, Beijing 100124, PR China;4. College of Materials Science and Engineering, Chongqing University, Chongqing 400044, PR China;5. Department of Physics and Astronomy, Shanghai Jiao Tong University, Shanghai 200240, PR China;6. Jozef Stefan Institute, Jamova 39, Ljubliana SI-1000, Slovenia, EU;7. School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology, Brisbane QLD 4000, Australia;8. CSIRO-QUT Joint Sustainable Processes and Devices Laboratory, Commonwealth Scientific and Industrial Research Organization, P.O. Box 218, Lindfield NSW 2070, Australia;1. Manchester Metropolitan University;2. Hungarian National Police;3. iTTi;4. European Dynamics |
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| Abstract: | Male Swiss mice were allowed to explore a novel environment, provided by an open-field activity chamber for a 10-min period. The procedure was repeated twice within a 24-h interval. The difference in the exploratory activity between the first (training) and the second exposure (testing) to the chamber was taken as an index of retention of this habituation task. Posttraining intraperitoneal administration of insulin (8, 20, or 80 IU/kg) impaired retention in a dose-related manner, although only the dose of 20 IU/kg of insulin produced significant effects. Thus, the dose–response curve adopted a U-shaped form. Insulin (20 IU/kg) given to untrained mice did not modify their exploratory performance when recorded 24 h later. The effects of insulin on retention were time dependent, suggesting an action on memory storage. An ineffective dose (8 IU/kg) of insulin given together with an ineffective dose of a central acting muscarinic cholinergic antagonist atropine (0.5 mg/kg) or with a central acting nicotinic cholinergic antagonist mecamylamine (5 mg/kg) interacted to impair retention. In contrast, neither methylatropine (0.5 mg/kg), a peripherally acting muscarinic receptor blocker, nor hexamethonium (5 mg/kg), a peripherally acting nicotinic receptor blocker, interacted with the subeffective dose of insulin on retention. The impairing effects of insulin (20 IU/kg) on retention were reversed by the simultaneous administration of physostigmine (70 μg/kg) but not neostigmine (70 μg/kg). We suggest that insulin impairs memory storage of one form of learning elicited by stimuli repeatedly presented without reinforcement, probably through a decrement of brain acetylcholine synthesis. |
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