Environmental Enrichment Prevents Methamphetamine-Induced Spatial Memory Deficits and Obsessive-Compulsive Behavior in Rats
Objective: This study was designed to examine the effect of environmental enrichment during methamphetamine (METH) dependency and withdrawal on methamphetamine-induced spatial learning and memory deficits and obsessive-compulsive behavior.
Method: Adult male Wistar rats (200 ± 10 g) chronically received bi-daily doses of METH (2 mg/kg, sc, with 12 hours intervals) for 14 days. Rats reared in standard (SE) or enriched environment (EE) during the development of dependence on METH and withdrawal. Then, they were tested for spatial learning and memory (the water maze), and obsessive-compulsive behavior as grooming behavior in METH-withdrawn rats.
Results: The results revealed that the Sal/EE and METH/EE rats reared in EE spent more time in the target zone on the water maze and displayed significantly increased proximity to the platform compared to their control groups. METH withdrawn rats reared in EE displayed less grooming behavior than METH/SE group.
Conclusion: Our findings revealed EE ameliorates METH-induced spatial memory deficits and obsessive-compulsive behavior in rats.
Swant J, Chirwa S, Stanwood G, Khoshbouei H. Methamphetamine reduces LTP and increases baseline synaptic transmission in the CA1 region of mouse hippocampus. PLoS One 2010; 5: e11382.
Stumm G, Schlegel J, Schafer T, Wurz C, Mennel HD, Krieg JC, et al. Amphetamines induce apoptosis and regulation of bcl-x splice variants in neocortical neurons. Faseb j 1999; 13: 1065-1072.
Hopkins KJ, Wang G, Schmued LC. Temporal progression of kainic acid induced neuronal and myelin degeneration in the rat forebrain. Brain Res 2000; 864: 69-80.
Johnson BA, Roache JD, Ait-Daoud N, Wells LT, Wallace CL, Dawes MA, et al. Effects of topiramate on methamphetamine-induced changes in attentional and perceptual-motor skills of cognition in recently abstinent methamphetamine-dependent individuals. Prog Neuropsychopharmacol Biol Psychiatry 2007; 31: 123-130.
Simoes PF, Silva AP, Pereira FC, Marques E, Grade S, Milhazes N, et al. Methamphetamine induces alterations on hippocampal NMDA and AMPA receptor subunit levels and impairs spatial working memory. Neuroscience 2007; 150: 433-441.
Schroder N, O'Dell SJ, Marshall JF. Neurotoxic methamphetamine regimen severely impairs recognition memory in rats. Synapse 2003; 49: 89-96.
Bigdeli I, Nikfarjam- Haftasia M, Miladi-Gorji H, Fadaei A. The spatial learning and memory performance in methamphetamine-sensitized and withdrawn rats. Iran J Basic Med Sci 2015; 18: 234-239.
Itzhak Y, Martin JL, Ali SF. Methamphetamine-induced dopaminergic neurotoxicity in mice: long-lasting sensitization to the locomotor stimulation and desensitization to the rewarding effects of methamphetamine. Prog Neuropsychopharmacol Biol Psychiatry 2002; 26: 1177-1183.
Qi J, Yang JY, Song M, Li Y, Wang F, Wu CF. Inhibition by oxytocin of methamphetamine-induced hyperactivity related to dopamine turnover in the mesolimbic region in mice. Naunyn Schmiedebergs Arch Pharmacol 2008; 376: 441-448.
Berridge KC, Aldridge JW, Houchard KR, Zhuang X. Sequential super-stereotypy of an instinctive fixed action pattern in hyper-dopaminergic mutant mice: a model of obsessive compulsive disorder and Tourette's. BMC Biol 2005; 3: 4.
Eilam D, Szechtman H. Psychostimulant-induced behavior as an animal model of obsessive-compulsive disorder: an ethological approach to the form of compulsive rituals. CNS Spectr 2005; 10: 191-202.
Gentry WB, Ghafoor AU, Wessinger WD, Laurenzana EM, Hendrickson HP, Owens SM. (+)-Methamphetamine-induced spontaneous behavior in rats depends on route of (+) METH administration. Pharmacol Biochem Behav 2004; 79: 751-760.
Greer JM, Capecchi MR. Hoxb8 is required for normal grooming behavior in mice. Neuron 2002; 33: 23-34.
Garland EL, Froeliger B, Howard MO. Mindfulness training targets neurocognitive mechanisms of addiction at the attention-appraisal-emotion interface. Front Psychiatry 2014; 4: 173.
Hajheidari S, Miladi-Gorji H, Bigdeli I. Effect of the environmental enrichment on the severity of psychological dependence and voluntary methamphetamine consumption in methamphetamine withdrawn rats. Neurosci Lett 2015; 584: 151-155.
Hajheidari S, Miladi-Gorji H, Bigdeli I. Effects of environmental enrichment during induction of methamphetamine dependence on the behavioral withdrawal symptoms in rats. Neurosci Lett 2015; 605: 39-43.
Escorihuela RM, Tobena A, Fernandez-Teruel A. Environmental enrichment and postnatal handling prevent spatial learning deficits in aged hypoemotional (Roman high-avoidance) and hyperemotional (Roman low-avoidance) rats. Learn Mem 1995; 2: 40-48.
Wright RL, Conrad CD. Enriched environment prevents chronic stress-induced spatial learning and memory deficits. Behav Brain Res 2008; 187: 41-47.
Nilsson M, Perfilieva E, Johansson U, Orwar O, Eriksson PS. Enriched environment increases neurogenesis in the adult rat dentate gyrus and improves spatial memory. J Neurobiol 1999; 39: 569-578.
Falkenberg T, Mohammed AK, Henriksson B, Persson H, Winblad B, Lindefors N. Increased expression of brain-derived neurotrophic factor mRNA in rat hippocampus is associated with improved spatial memory and enriched environment. Neurosci Lett 1992; 138: 153-156.
Miladi-Gorji H, Rashidy-Pour A, Fathollahi Y, Akhavan MM, Semnanian S, Safari M. Voluntary exercise ameliorates cognitive deficits in morphine dependent rats: the role of hippocampal brain-derived neurotrophic factor. Neurobiol Learn Mem 2011; 96: 479-491.
Georgiadou G, Tarantilis PA, Pitsikas N. Effects of the active constituents of Crocus Sativus L., crocins, in an animal model of obsessive-compulsive disorder. Neurosci Lett 2012; 528: 27-30.
Graf M, Kantor S, Anheuer ZE, Modos EA, Bagdy G. m-CPP-induced self-grooming is mediated by 5-HT2C receptors. Behav Brain Res 2003; 142: 175-179.
Akhavan MM, Miladi-Gorji H, Emami-Abarghoie M, Safari M, Sadighi-Moghaddam B, A AV, et al. Maternal Voluntary Exercise during Pregnancy Enhances the Spatial Learning Acquisition but not the Retention of Memory in Rat Pups via a TrkB-mediated Mechanism: The Role of Hippocampal BDNF Expression. Iran J Basic Med Sci 2013; 16: 955-961.
Cui M, Yang Y, Yang J, Zhang J, Han H, Ma W, et al. Enriched environment experience overcomes the memory deficits and depressive-like behavior induced by early life stress. Neurosci Lett 2006; 404: 208-212.
Bennett JC, McRae PA, Levy LJ, Frick KM. Long-term continuous, but not daily, environmental enrichment reduces spatial memory decline in aged male mice. Neurobiol Learn Mem 2006; 85: 139-152.
Zakharova E, Miller J, Unterwald E, Wade D, Izenwasser S. Social and physical environment alter cocaine conditioned place preference and dopaminergic markers in adolescent male rats. Neuroscience 2009; 163: 890-897.
Lee EH, Hsu WL, Ma YL, Lee PJ, Chao CC. Enrichment enhances the expression of sgk, a glucocorticoid-induced gene, and facilitates spatial learning through glutamate AMPA receptor mediation. Eur J Neurosci 2003; 18: 2842-2852.
Beauquis J, Pavia P, Pomilio C, Vinuesa A, Podlutskaya N, Galvan V, et al. Environmental enrichment prevents astroglial pathological changes in the hippocampus of APP transgenic mice, model of Alzheimer's disease. Exp Neurol 2013; 239: 28-37.
Steiner B, Winter C, Hosman K, Siebert E, Kempermann G, Petrus DS, et al. Enriched environment induces cellular plasticity in the adult substantia nigra and improves motor behavior function in the 6-OHDA rat model of Parkinson's disease. Exp Neurol 2006; 199: 291-300.
Hockly E, Cordery PM, Woodman B, Mahal A, van Dellen A, Blakemore C, et al. Environmental enrichment slows disease progression in R6/2 Huntington's disease mice. Ann Neurol 2002; 51: 235-242.
Wooters TE, Bardo MT, Dwoskin LP, Midde NM, Gomez AM, Mactutus CF, et al. Effect of environmental enrichment on methylphenidate-induced locomotion and dopamine transporter dynamics. Behav Brain Res 2011; 219: 98-107.
Turner CA, Yang MC, Lewis MH. Environmental enrichment: effects on stereotyped behavior and regional neuronal metabolic activity. Brain Res 2002; 938: 15-21.
Brenes JC, Rodriguez O, Fornaguera J. Differential effect of environment enrichment and social isolation on depressive-like behavior, spontaneous activity and serotonin and norepinephrine concentration in prefrontal cortex and ventral striatum. Pharmacol Biochem Behav 2008; 89: 85-93.
Turner CA, Lewis MH, King MA. Environmental enrichment: effects on stereotyped behavior and dendritic morphology. Dev Psychobiol 2003; 43: 20-27.
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