Abstract
Environmental enrichment (EE) has been shown to produce beneficial effects in animal models of a wide variety of neurological and psychiatric disorders. EE exhibits antidepressant function; reduces anxiety, improves spatial learning and memory impairment. EE can reduce sensitivity to loss of reward by reducing frustration-like emotional states and facilitates the extinction of conditioned fear. However, some studies related to the emotional effects of EE present controversial results such as reduction or increase in anxiety. The time of exposure to an enriched environment seems to be an important factor in the behavioral responses presented by animals subjected to aversive stimuli. The present study compared the effects of two and four week exposure to EE with young adult Wistar rats under the same conditions and protocol on fear behavioral parameters in the face of footshock (unconditioned fear) and on re-exposure to an environment after electrical shock pairing (conditioned fear). We showed that the EE with a duration of two weeks reduced the freezing response of the animals in an unconditioned fear situation, that is, with the aversive stimulus present in the environment, however, did not influence the same behavior in a conditioned fear situation. In addition, the short-term EE developed the locomotor and exploratory activity, identified by the high rearing behavior, which may also suggest a low level of anxiety in these animals. We can conclude that EE changes the unconditioned fear responses of young adult rats. In addition, the duration of EE interferes differently, being two weeks of treatment with EE sufficient to cause improvement in coping with unconditioned aversive situations. We suggest that the emotional benefits resulting from the welfare provided by EE can be abolished by the longer duration of this treatment, due to the already known effect of tolerance to lasting or abundant rewards.
References
- ANTONIADIS, E.A.; MCDONALD, R.J. Amygdala, hippocampus, and unconditioned fear. Experimental Brain Research. 138:200-209, 2001.
- BLANCHARD, R.J., BLANCHARD, D.C. Innate and conditioned reactions to threat in rats with amygdaloid lesions. J Comp Physiol Psychol. 372: 281–290, 1972.
- BLANCHARD, D.C.; BLANCHARD, R.J. Crouching as an index of fear. J Comp Physiol Psychol. 67: 370-5, 1969.
- BLANCHARD, D.C. et al. (editores). Handbook of anxiety and fear. Elsevier Sciense, p.63–79, 2008.
- BOERNGEN-LACERDA, R.; SOUZA-FORMIGONI, M.L.O. Does the increase in locomotion induced by ethanol indicate its stimulant or anxiolytic properties? Pharmacology Biochemistry and Behavior, 67: 225-232, 2000. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032934/
- BRANDÃO, M.L. et al. Neural organization of different types of fear: implications for the understanding of anxiety. Rev Bras Psiquiatr. 25: 36-41, 2003.
- BURMAN, O.H.P.; PARKER, R.M.A.; PAUL,E.S.; MENDL, M. Sensitivity to reward loss as a indicator of animal emotion and welfare. Biol. Lett. 4: 330-333, 2008. Available from: http://rsbl.royalsocietypublishing.org/content/4/4/330
- CAMPÊLO, C.L.C. et al. Exposure to an enriched environment facilitates motor recovery and prevents short-term memory impairment and reduction of striatal BDNF in a progressive pharmacological model of parkinsonism in mice. Behavioural Brain Research. 328: 138-148, 2017. Available from: http://www.sciencedirect.com/science/article/pii/S0166432817306599
- COPPENS, C.M.; BOER, S.F.; KOOLHAAS, J.M. Coping styles and behavioural flexibility: towards underlying mechanisms. Philosophical Transactions of the Royal Society of London B: Biological Sciences, 365:4021-4028, 2010. Available from: http://rstb.royalsocietypublishing.org/content/365/1560/4021
- CURZON, P.; RUSTAY, N.R.; BROWMAN, K.E. Cued and contextual fear conditioning for rodents. In: BUCCAFUSCO, J.J. (ed). Methods of behavior analysis in neuroscience, 2nd edition, Boca Raton, FL: CRC Press, p.26–49, 2009. Available from: https://www.ncbi.nlm.nih.gov/books/NBK5223/#!po=1.92308
- DAVID, J.T. et al. A neural network underlying individual differences in emotion and aggression in male golden hamsters. Neuroscience, 126:567-578, 2004. Available from: http://www.sciencedirect.com/science/article/pii/S0306452204002714
- DEL ARCO, A. et al. Stress, prefrontal cortex and environmental enrichment: studies on dopamine and acetylcholine release and working memory performance in rats. Behavioural brain research.176: 267-273, 2007. Available from: https://www.ncbi.nlm.nih.gov/pubmed/17097747
- FAHERTY, C.J.; KERLEYA, D.; SMEYNE, R.J. A Golgi-Cox morphological analysis of neuronal changes induced by environmental enrichment. Rev Brain Res., 141:55-61, 2003. Available from: http://www.sciencedirect.com/science/article/pii/S0165380602006429
- FISCHER, A.; SANANBENESI, F.; WANG, X.; DOBBIN, M.; TSAI, L.H. Recovery of learning and memory is associated with chromatin remodelling. Nature. 447:178-183, 2007. Available from: https://www.nature.com/nature/journal/v447/n7141/full/nature05772.html
- FOLWEILER, K.A. et al. Combining the antipsychotic drug haloperidol and environmental enrichment after traumatic brain injury is a double-edged sword. Journal of neurotrauma, 34: 451-458, 2017. Available from: http://online.liebertpub.com/doi/full/10.1089/neu.2016.4417
- GOES, T.C.; ANTUNES, F.D.; TEIXEIRA-SILVA, F. Environmental enrichment for adult rats: Effects on trait and state anxiety. Neuroscience Letters. 584:93–96, 2015. Available from: http://dx.doi.org/10.1016/j.neulet.2014.10.004
- GRUPE, D.W.; NITSCHKE, J.B. Uncertainty and anticipation in anxiety: an integrated neurobiological and psychological perspective. Nature Rev. Neurosci. 14:488–501, 2013.
- ICKES, B.R.; PHAM, T.M.; SANDERS, L.A.; ALBECK, D.S.; MOHAMMED, A.H.; GRANHOLM, A.C. Longterm environmental enrichment leads to regional increases in neurotrophin levels in rat brain. Exp Neurol, 164:45–52, 2000. Available from: http://www.sciencedirect.com/science/article/pii/S0014488600974156
- IWATA, J.; LEDOUX, J.E. Dissociation of associative and nonas- sociative concommitants of classical fear conditioning in the freely behaving rat. Behav Neurosci. 102:66–76, 1988.
- JUNGLING, A. et al. Effects of postnatal enriched environment in a model of parkinson’s disease in adult rats. Int. J. Mol. Sci. 18: 406, 2017. Available from: http://www.mdpi.com/1422-0067/18/2/406/htm
- KANDEL, E.R. et al. PrincÃpios de neurociências. 5.ed. Porto Alegre: AMGH, 2014.
- KEMPERMANN, G.; KUHN, H.G.; GAGE, F.H. More hippocampal neurons in adult mice living in an enriched environment. Nature. 386:493–5, 1997. Available from: http://www.nature.com/nature/journal/v386/n6624/pdf/386493a0.pdf
- KOOLHAAS, J. M. et al. Coping styles in animals: current status in behavior and stress-physiology. Neuroscience & Biobehavioral Reviews, 23:925-935, 1999. Available from: http://www.sciencedirect.com/science/article/pii/S0149763499000263
- LACERDA, G.F.M.L. Ansiedade em modelos animais: Efeito de drogas nas dimensões extraÃdas da análise fatorial. Curitiba. 2006. Tese de Doutorado. Dissertação [Mestrado em Farmacologia]. Universidade Federal do Paraná. Available from:
- http://www.acervodigital.ufpr.br/bitstream/handle/1884/3780/Lacerda%20GFML%202006.pdf?sequence=1&isAllowed=y
- LACH, G. et al. Short-term enriched environment exposure facilitates fear extinction in adult rats: The NPY-Y1 receptor modulation. Neuropeptides. 55:73 – 78, 2015. Available from: http://www.neuropeptidesjournal.com/article/S0143-4179(15)00101-8/pdf
- LANDGRAF, R.; WIGGER, A. High vs low anxiety-related behavior rats: an animal model of extremes in trait anxiety. Behavior genetics, 32: 301-314, 2002. Available from: https://link.springer.com/article/10.1023%2FA%3A1020258104318?LI=true
- LEARY, J.B.; BONDI, C.O.; LAPORTE, M.J.; CARLSON, L.J.; RADABAUGH, H.L.; CHENG, J.P.; KLINE, A.E. The therapeutic efficacy of environmental enrichment and methylphenidate alone and in combination after controlled cortical impact injury. Journal of neurotrauma, 34: 444-450, 2017. Available from: http://online.liebertpub.com/doi/full/10.1089/neu.2016.4438
- LEDOUX, J.E. Emotion circuits in the brain. Annu. Rev. Neurosci. 23:155–184, 2000.
- LEDOUX, J.E. Coming to terms with fear. Proc. Natl Acad. Sci. USA. 111:2871–2878, 2014.
- LEGER, M. et al. Environmental enrichment duration differentially affects behavior and neuroplasticity in adult mice. Cerebral cortex. 25:4048-4061, 2015. Available from: https://academic.oup.com/cercor/article/25/11/4048/2366269/Environmental-Enrichment-Duration-Differentially
- MOSER, M.B.; TROMMALD, M.; ANDERSEN, P. An increase in dendritic spine density on hippocampal ca1 pyramidal cells following spatial learning in adult rats suggests the formation of new synapses. Proc Natl Acad Sci USA . 91:12673–5, 1994. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC45501/pdf/pnas01477-0328.pdf
- NITHIANANTHARAJAH, J.; HANNAN, A.J. Enriched environments, experience-dependent plasticity and disorders of the nervous system. Nat Rev Neurosci. 7: 697–709, 2006. Available from: http://www.nature.com/nrn/journal/v7/n9/full/nrn1970.html
- PAWLAK, C.R.; SCHWARTING, R.KW. Object preference and nicotine consumption in rats with high vs. low rearing activity in a novel open field. Pharmacology Biochemistry and Behavior, 73:679-687, 2002. Available from: http://www.sciencedirect.com/science/article/pii/S0091305702008523
- PHELPS, E.A.; LEDOUX, J.E. Contributions of the amygdala to emotion processing: from animal models to human behavior. Neuron, 48:175–187, 2005. Available from: http://www.cell.com/neuron/pdf/S0896-6273(05)00823-8.pdf
- PIZZORUSSO, T.; BERARDI, N.; MAFFEI, L. A richness that cures. Neuron. 54: 508–10, 2007. Available from: http://www.sciencedirect.com/science/article/pii/S0896627307003376
- RAY, J.; HANSEN, S. Temperament in the rat: sex differences and hormonal influences on harm avoidance and novelty seeking. Behavioral neuroscience, 118:488, 2004. Available from: http://dx.doi.org/10.1037/0735-7044.118.3.488
- RIBEIRO, A.M.; BARBOSA, F.F.; GODINHO, M.R.; FERNANDES, V.S.; MUNGUBA, H.; MELO, T.G.; SILVA, R.H. Sex differences in aversive memory in rats: possible role of extinction and reactive emotional factors. Brain Cogn. 74:145–151, 2010. Available from: http://dx.doi.org/10.1016/j.bandc.2010.07.012
- RONZONI, G.; ANTÓN, M.; MORA, F.; SEGOVIA, G.; DEL ARCO, A. Infralimbic cortex controls the activity of the hypothalamus–pituitary–adrenal axis and the formation of aversive memory: effects of environmental enrichment. Behavioural brain research. 297: 338-344, 2016. Available from: http://www.sciencedirect.com/science/article/pii/S0166432815302515
- ROSSI, C.; ANGELUCCI, A.; COSTANTIN, L.; BRASCHI, C.; MAZZANTINI, M.; BABBINI, F.; et al. Brainderived neurotrophic factor (bdnf) is required for the enhancement of hippocampal neurogenesis following environmental enrichment. Eur J Neuro Sci, 24:1850–6, 2006. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17040481
- SCHULTZ, W. Neuronal reward and decision signal: from theories to data. Physiol Rev, 95:853–951, 2015. Available from: http://physrev.physiology.org/cgi/pmidlookup?view=long&pmid=26109341
- SMITH, B.L.; LYONS, C.E.; CORREA, F.G.; BENOIT, S.C.; MYERS, B.; SOLOMON, M.B.; HERMAN, J.P. Behavioral and physiological consequences of enrichment loss in rats. Psychoneuroendocrinology. 77: 37-46, 2017. Available from: http://www.sciencedirect.com/science/article/pii/S0306453016304279
- SHILPA, B.M.; BHAGYA, V.; HARISH, G.; BHARATH, M.S.; RAO, B.S. Environmental enrichment ameliorates chronic immobilisation stress-induced spatial learning deficits and restores the expression of BDNF, VEGF, GFAP and glucocorticoid receptors. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 76: 88-100, 2017. Available from: http://www.sciencedirect.com/science/article/pii/S027858461630197X
- SPRUIJT, B.M.; BOS, R.V.D.; PIJLMAN, F.T.A. A concept of welfare based on reward evaluating mechanisms in the brain: anticipatory behaviour as an indicator for the state of reward systems. Applied Animal Behaviour Science, 72:145–171, 2001. Available from: http://www.sciencedirect.com/science/article/pii/S0168159100002045
- STEIMER, T. Animal models of anxiety disorders in rats and mice: some conceptual issues. Dialogues in clinical neuroscience, 13:495, 2011. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3263396/
- TOVOTE, P.; FADOK, J.P.; LUTHI, A. Neuronal circuits for fear and anxiety. Nature.16:317-331, 2015. Available from: http://www.nature.com/nrn/journal/v16/n6/full/nrn3945.html
- VAN DE WEERD, H.A.; BAUMANS, V.; KOOLHAAS, J.M.; VANZUTPHEN, L.F.M. Strain specific behavioural response to environmental enrichment in the mouse. Journal of Experimental Animal Science. 36:117–27, 1994.
- VIANNA, D.M.L.; LANDEIRA-FERNANDEZ, J.; BRANDÃO, M.L. Dorsolateral and ventral regions of the periaqueductal gray matter are involved in distinct types of fear. Neurosci Biobehav Rev. 5,:711-9, 2001.
- XIE, H. et. al. Enrichment-induced exercise to quantify the effect of different housing conditions: A tool to standardize enriched environment protocols. Behavioural Brain Research. 249:81– 89, 2013. Available from: http://dx.doi.org/10.1016/j.bbr.2013.04.032