title: Effects of voluntary and treadmill exercise on spontaneous withdrawal signs, cognitive deficits and alterations in apoptosis-associated proteins in morphine-dependent rats.
abstract: Chronic exposure to morphine results in cognitive deficits and alterations of apoptotic proteins in favor of cell death in the hippocampus, a brain region critically involved in learning and memory. Physical activity has been shown to have beneficial effects on brain health. In the current work, we examined the effects of voluntary and treadmill exercise on spontaneous withdrawal signs, the associated cognitive defects, and changes of apoptotic proteins in morphine-dependent rats. Morphine dependence was induced through bi-daily administrations of morphine (10mg/kg) for 10 days. Then, the rats were trained under two different exercise protocols: mild treadmill exercise or voluntary wheel exercise for 10 days. After exercise training, their spatial learning and memory and aversive memory were examined by a water maze and by an inhibitory avoidance task, respectively. The expression of the pro-apoptotic protein Bax and the anti-apoptotic protein Bcl-2 in the hippocampus were determined by immunoblotting. We found that chronic exposure to morphine impaired spatial and aversive memory and remarkably suppressed the expression of Bcl-2, but Bax expression remained constant. Both voluntary and treadmill exercise alleviated memory impairment, increased the expression of Bcl-2 protein, and only the later suppressed the expression of Bax protein in morphine-dependent animals. Moreover, both exercise protocols diminished the occurrence of spontaneous morphine withdrawal signs. Our findings showed that exercise reduces the spontaneous morphine-withdrawal signs, blocks the associated impairment of cognitive performance, and overcomes morphine-induced alterations in apoptotic proteins in favor of cell death. Thus, exercise may be a useful therapeutic strategy for cognitive and behavioral deficits in addict individuals.
authors.affiliation: Laboratory of Learning and Memory, Research Center and Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
authors.forename: Amin
authors.initials: A
authors.lastname: Mokhtari-Zaer
authors.affiliation: Laboratory of Learning and Memory, Research Center and Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
authors.forename: Shahrbanoo
authors.initials: S
authors.lastname: Ghodrati-Jaldbakhan
authors.affiliation: Laboratory of Learning and Memory, Research Center and Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
authors.forename: Abbas Ali
authors.initials: AA
authors.lastname: Vafaei
authors.affiliation: Laboratory of Learning and Memory, Research Center and Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Miladi-Gorji
authors.affiliation: Skin Research Center, Laboratory of Protein and Enzyme, ShahidBeheshti University (M.C.), Shohada-e Tajrish Hospital, Shahrdari St., 1989934148 Tehran, Iran.
authors.forename: Maziar M
authors.initials: MM
authors.lastname: Akhavan
authors.affiliation: Laboratory of Learning and Memory, Research Center and Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran; Skin Research Center, Laboratory of Protein and Enzyme, ShahidBeheshti University (M.C.), Shohada-e Tajrish Hospital, Shahrdari St., 1989934148 Tehran, Iran.
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Bandegi
authors.affiliation: Laboratory of Learning and Memory, Research Center and Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran. Electronic address: Rashidy-pour@semums.ac.ir.
authors.forename: Ali
authors.initials: A
authors.lastname: Rashidy-Pour
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects / Q000378:metabolism*; D001362:Avoidance Learning / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D009020:Morphine / Q000009:adverse effects / Q000494:pharmacology; D009021:Morphine Dependence / Q000209:etiology / Q000378:metabolism / Q000523:psychology* / Q000628:therapy*; D009043:Motor Activity / Q000187:drug effects*; D010805:Physical Conditioning, Animal / Q000379:methods / Q000502:physiology / Q000523:psychology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D051017:Apoptosis Regulatory Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D009020:Morphine
keywords: Apoptosis; Chronic morphine; Cognitive defect; Treadmill exercise; Voluntary exercise