Nicotina y modelos animales: ¿qué nos aporta el paradigma de enriquecimiento ambiental? Nicotine and animal models: what does the environmental enrichment paradigm tell us?

Autores/as

  • Patricia Mesa-Gresa Departamento de Psicobiología. Facultad de Psicología. Universitat de València.
  • Asunción Pérez-Martínez Departamento de Psicobiología. Facultad de Psicología. Universitat de València.
  • Rosa Redolat-Iborra Departamento de Psicobiología. Facultad de Psicología. Universitat de València. Enviar correspondencia a: Rosa Redolat Iborra. Departamento de Psicobiología. Facultad de Psicología. Universitat de València. Avda. Blasco Ibáñez 21. 46010 Valencia.

DOI:

https://doi.org/10.20882/adicciones.100

Palabras clave:

Enriquecimiento ambiental, adicción, nicotina, drogas de abuso, ratones Environmental Enrichment, addiction, nicotine, drugs of abuse, mice

Resumen

El Enriquecimiento Ambiental (Environmental Enrichment o EE) es un modelo de alojamiento basada en la estimulación a nivel físico, cognitivo y sensorial de roedores. Esta condición se caracteriza por el alojamiento de un grupo de animales en cajas grandes que contienen distintos objetos como túneles, juguetes y ruedas de correr. El principal objetivo del presente trabajo es plantear los principales argumentos que sugieren que el alojamiento en condiciones de EE puede disminuir la vulnerabilidad a desarrollar adicción a la nicotina y a otras drogas de abuso, así como revisar estudios experimentales recientes relacionados con este área. Con este fin, se presenta una revisión de los principales cambios inducidos por el EE a nivel físico, neurobiológico y conductual y se exponen los resultados obtenidos en diversos estudios recientes que indican que el alojamiento en EE induce cambios neuroquímicos (potenciación del aumento de liberación de dopamina inducida por la nicotina en el córtex cerebral) y conductuales (mayor capacidad para discriminar la presencia de recompensa y disminución de la impulsividad) que apoyarían la hipótesis planteada. En base a estos resultados, cabría proponer el EE como un modelo adecuado para el estudio de la vulnerabilidad a la adicción a diferentes drogas de abuso como la cocaína o la nicotina aunque es necesario realizar más estudios que permitan establecer las bases neurobiológicas de los efectos inducidos por la exposición a ambientes enriquecidos y su posible relación con modificaciones en los sistemas cerebrales de refuerzo.
The Environmental Enrichment (EE) paradigm is a housing condition which aims is to provide physical, cognitive and sensorial stimulation to rodents. Animals are housed in larger cages containing inanimate objects such as tunnels, toys and running wheels. The main aim of the current work is to tackle the arguments which suggest that EE may diminish vulnerability to developing addiction to nicotine and other drugs of abuse and to review recent experimental studies performed in relation to this subject. We discuss the major changes induced by EE at physical, neurobiological and behavioral levels and review the results of recent studies which indicate that EE promotes both neurochemical (potentiation of the increase in dopamine release induced by nicotine in the brain cortex) and behavioral changes (increased ability to discriminate the presence of reward and decreased impulsivity), thus supporting the hypothesis put forward. In light of these results, EE can be proposed as a model for the study of vulnerability to addiction to different drugs of abuse, including cocaine and nicotine, though further studies are needed in order to establish the neurobiological implications of the effects of exposure to enriched environments and their possible relationship with changes in brain reward systems..

Biografía del autor/a

Patricia Mesa-Gresa, Departamento de Psicobiología. Facultad de Psicología. Universitat de València.

Citas

Arndt, S. S., Laarakker, M. C., van Lith, H. A., van der Staay, F. J., Gieling, E., Salomons, A. R.,…Ohl, F. (2009). Individual housing of mice: impact on behaviour and stress responses. Physiology& Behavior, 97, 385-

doi:10.1016/j.physbeh.2009.03.008.

Bardo, M. T., Bowling, S. L., Rowlett, J. K., Manderscheid, P., Buxton, S.

T., y Dwoskin, L. P. (1995). Environmental enrichment attenuates locomotor sensitization, but not in vitro dopamine release, induced by amphetamine. Pharmacology, Biochemistry & Behavior, 51, 397-405. doi:10.1016/0091-3057(94)00413-D.

Bardo, M. T., Klebaur, J. E., Valone, J. M., y Deaton, C. (2001). Environmental enrichment decreases intravenous self-administration of amphetamine in female and male rats. Psychopharmacology, 155, 278-284. doi:10.1007/s002130100720.

Beauquis, J., Roig, P., De Nicola, A. F., y Saravia, F. (2010). Short-term

environmental enrichment enhances adult neurogenesis, vascular network and dendritic complexity in the hippocampus of type 1 diabetic mice. PloS One, 5, e13993. doi:10.1371/journal.pone.0013993.

Bennett, J. C., McRae, P. A., Levy, L. J., y Frick, K. M. (2006). Long-term

continuous, but not daily, environmental enrichment reduces spatial memory decline in aged male mice. Neurobiology of Learning and Memory, 85, 139-152. doi:10.1016/j.nlm.2005.09.003.

Bezard, E., Dovero, S., Belin, D., Duconger, S., Jackson-Lewis, V.,

Przedborski, S., ... Jaber, M. (2003). Enriched environment confers resistance to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and cocaine: Involvement of dopamine transporter and trophic factors. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 23, 10999-11007.

Bowling, S.L., y Bardo, M.T. (1994). Locomotor and rewarding effects of amphetamine in enriched, social, and isolated reared rats. Pharmacology, Biochemistry & Behavior, 48, 459-64. doi:10.1016/0091-3057(94)90553-3.

Brenes, J. C., Padilla, M., y Fornaguera, J. (2009). A detailed analysis

of open-field habituation and behavioral and neurochemical antidepressant-like effects in postweaning enriched rats. Behavioural

Brain Research, 197, 125-137. doi:10.1016/j.bbr.2008.08.014.

Burrows, E. L., McOmish, C. E., y Hannan, A. J. (2010). Gene-environment

interactions and construct validity in preclinical models of psychiatric disorders. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 35, 1376-1382. doi:10.1016/j.pnpbp.2010.12.011.

Carvalho, A. F., Araujo, A. J., Farias, D. F., Rocha-Bezerra, L. C., y

Cavalheiro, M. G. (2009). Development and reproductive performance of swiss mice in an enriched environment. Brazilian Journal of Biology, 69, 153-160.

Carroll, M. E., Anker, J. J., y Perry, J. L. (2009). Modeling risk factors

for nicotine and other drug abuse in the preclinical laboratory. Drug and Alcohol Dependence, 104, S70-78. doi:10.1016/j.drugalcdep.2008.11.011.

Chauvet, C., Lardeux, V., Goldberg, S. R., Jaber, M., y Solinas, M. (2009). Environmental enrichment reduces cocaine seeking and reinstatement induced by cues and stress but not by cocaine. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 34, 2767-2778.doi:10.1038/npp.2009.127.

Chen, Y., Mao, Y., Zhou, D., Hu, X., Wang, J., y Ma, Y. (2010). Environmental enrichment and chronic restraint stress in ICR mice: Effects on prepulse inhibition of startle and Y-maze spatial recognition memory. Behavioural Brain Research, 212, 49-55. doi:10.1016/j.bbr.2010.03.033.

Coolon, R. A., y Cain, M. E. (2009). Individual differences in response to novelty and the conditioned locomotor effects of nicotine. Behavioural Pharmacology, 20, 322-329. doi:10.1097/FBP.0b013e32832f0176.

De Biasi, M., y Dani, J.A. (2011). Reward, addiction, withdrawal to nicotine. Annual Review of Neuroscience, 34: 105-30. doi:10.1146/

annurev-neuro-061010-113734.

Diamond, M. C. (2001). Response of the brain to enrichment. Anais Da

Academia Brasileira De Ciencias, 73, 211-220. doi:10.1590/S0001-

El Rawas, R., Thiriet, N., Lardeux, V., Jaber, M., y Solinas, M. (2009).

Environmental enrichment decreases the rewarding but not the activating effects of heroin. Psychopharmacology, 203, 561-570. doi:10.1007/s00213-008-1402-6.

El Rawas, R., Thiriet, N., Nader, J., Lardeux, V., Jaber, M., y Solinas, M. (2011). Early exposure to environmental enrichment alters the expression of genes of the endocannabinoid system. Brain Research, 1390, 80-89. doi:10.1016/j.brainres.2011.03.025.

Foscarin, S., Rossi, F., y Carulli, D. (2011). Influence of the environment

on adult CNS plasticity and repair. Cell Tissue Research, In press.

doi:10.1007/s00441-011-1293-4.

García-Fernández, G., Secades-Villa, R., García-Rodríguez, O., Alvarez-

López, H., Fernández-Hermida, J.R., Fernández-Artamendi, S., y Higgins, S.T. (2011). Long-term benefits of adding incentives to the community reinforcement approach for cocaine dependence. European Addiction Research, 17, 139-145. doi:10.1159/000324848.

Green, T. A., Alibhai, I. N., Roybal, C. N., Winstanley, C. A., Theobald, D. E., Birnbaum, S. G., … Nestler, E. J. (2010). Environmental enrichment produces a behavioral phenotype mediated by low cyclic adenosine monophosphate response element binding (CREB) activity in the nucleus accumbens. Biological Psychiatry, 67, 28-35. doi:10.1016/j.biopsych.2009.06.022.

Green, T. A., Cain, M. E., Thompson, M., y Bardo, M. T. (2003).

Environmental enrichment decreases nicotine-induced hyperactivity in rats. Psychopharmacology, 170, 235-241. doi:10.1007/s00213-003-1538-3.

Green, T. A., Gehrke, B. J., y Bardo, M. T. (2002). Environmental enrichment decreases intravenous amphetamine selfadministration in rats: Dose-response functions for fixed- and progressive-ratio schedules. Psychopharmacology, 162, 373-378. doi:10.1007/s00213-002-1134-y.

Grimm, J. W., Osincup, D., Wells, B., Manaois, M., Fyall, A., Buse, C., y Harkness, J. H. (2008). Environmental enrichment attenuates cue-induced reinstatement of sucrose seeking in rats. Behavioural Pharmacology, 19, 777-785. doi:10.1097/FBP.0b013e32831c3b18.

Hamilton, D. A., y Kolb, B. (2005). Differential effects of nicotine and complex housing on subsequent experience-dependent structural plasticity in the nucleus accumbens. Behavioral Neuroscience, 119, 355-365. doi:10.1037/0735-7044.119.2.355.

Hannigan, J. H., O’leary-Moore, S. K., y Berman, R. F. (2007). Postnatal

environmental or experiential amelioration of neurobehavioral effects of perinatal alcohol exposure in rats. Neuroscience and Biobehavioral Reviews, 31, 202-211. doi:10.1016/j.neubiorev.2006.06.019.

Hellemans, K. G., Nobrega, J. N., y Olmstead, M. C. (2005). Early environmental experience alters baseline and ethanol-induced cognitive impulsivity: Relationship to forebrain 5-HT1A receptor binding. Behavioural Brain Research, 159, 207-220. doi:10.1016/j.bbr.2004.10.018.

Ilin, Y., y Richter-Levin, G. (2009). Enriched environment experience

overcomes learning deficits and depressive-like behavior induced by juvenile stress. PloS One, 4, e4329. doi:10.1371/journal.pone.0004329.

Kempermann, G., Fabel, K., Ehninger, D., Babu, H., Leal-Galicia, P., Garthe, A., y Wolf, S. A. (2010). Why and how physical activity promotes experience-induced brain plasticity. Frontiers in Neuroscience, 4, 189. doi:10.3389/fnins.2010.00189.

Laviola, G., Hannan, A. J., Macri, S., Solinas, M., y Jaber, M. (2008). Effects

of enriched environment on animal models of neurodegenerative diseases and psychiatric disorders. Neurobiology of Disease, 31, 159-168. doi:10.1016/j.nbd.2008.05.001.

Lee, V., y Hoaken, P. N. (2007). Cognition, emotion, and neurobiological development: Mediating the relation between maltreatment and aggression. Child Maltreatment, 12, 281-298. doi:10.1177/1077559507303778.

Lopez, M. F., Doremus-Fitzwater, T. L., y Becker, H. C. (2010). Chronic

social isolation and chronic variable stress during early development induce later elevated ethanol intake in adult C57BL/6J mice. Alcohol

(Fayetteville, N.Y.), 45, 355-364. doi:10.1016/j.alcohol.2010.08.017.

Magalhaes, A., Summavielle, T., Tavares, M. A., y de Sousa, L. (2007).

Postnatal exposure to cocaine in rats housed in an enriched environment: Effects on social interactions. Human & Experimental Toxicology, 26, 303-309. doi:10.1177/0960327106070458.

Mesa-Gresa, P., Pérez-Martínez, A., y Redolat, R. (2009, septiembre).

Cambios emocionales inducidos por el enriquecimiento ambiental combinado con administración crónica de nicotina en ratones. Póster

presentado en el XIII Congreso Sociedad Española de Neurociencia,

Tarragona (España).

Mesa-Gresa, P., Pérez-Martínez, A., y Redolat, R. (2010, julio). A

comparison of behavior in NMRI male mice in enriched environments and isolation-housing. Póster presentado en el 7th FENS Forum of European Neuroscience, Amsterdam (Holanda).

Mesa-Gresa, P., y Moya-Albiol, L. (2011). Neurobiology of child abuse:

The ‘cycle of violence’. Revista De Neurología, 52, 489-503.

Meshi, D., Drew, M. R., Saxe, M., Ansorge, M. S., David, D., Santarelli,

L., … Hen, R.(2006). Hippocampal neurogenesis is not required for behavioral effects of environmental enrichment. Nature Neuroscience, 9, 729-731. doi:10.1038/nn1696.

Nithianantharajah, J., y Hannan, A. J. (2006). Enriched environments,

experience-dependent plasticity and disorders of the nervous system. Nature Reviews.Neuroscience, 7, 697-709. doi:10.1038/nrn1970.

Nithianantharajah, J., y Hannan, A. J. (2009). The neurobiology of brain and cognitive reserve: Mental and physical activity as modulators of brain disorders. Progress in Neurobiology, 89, 369-382. doi:10.1016/j.pneurobio.2009.10.001.

Nithianantharajah, J., y Hannan, A. J. (2011). Mechanisms mediating brain

and cognitive reserve: Experience-dependent neuroprotection and functional compensation in animal models of neurodegenerative diseases. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 35, 331-339. doi:10.1016/j.pnpbp.2010.10.026.

Peña, Y., Prunell, M., Dimitsantos, V., Nadal, R., y Escorihuela, R. M. (2006). Environmental enrichment effects in social investigation in rats are gender dependent. Behavioural Brain Research, 174, 181-187. doi:10.1016/j.bbr.2006.07.007.

Perry, J. L., Stairs, D. J., y Bardo, M. T. (2008). Impulsive choice and

environmental enrichment: Effects of d-amphetamine and methylphenidate. Behavioural Brain Research, 193, 48-54. doi:10.1016/j.bbr.2008.04.019.

Pietropaolo, S., Feldon, J., Alleva, E., Cirulli, F., y Yee, B. K. (2006). The

role of voluntary exercise in enriched rearing: A behavioral analysis. Behavioral Neuroscience, 120, 787-803. doi:10.1037/0735-7044.120.4.787.

Pizzorusso, T., Berardi, N., y Maffei, L. (2007). A richness that cures. Neuron, 54, 508-510. doi:10.1016/j.neuron.2007.05.003.

Puhl, M.D., Blum, J.S., Acosta-Torres, S., y Grigson, P.S. (2012).

Environmental enrichment protects against the acquisition of cocaine self-administration in adult male rats, but does not eliminate avoidance of a drug-associated saccharin cue. Behavioral Pharmacology, 23, 43-53. doi:10.1097/FBP.0b013e32834eb060.

Redolat, R., Perez-Martinez, A., Carrasco, M. C., y Mesa, P. (2009).

Individual differences in novelty-seeking and behavioral responses to nicotine: A review of animal studies. Current Drug Abuse Reviews, 2, 230-242.

Redolat, R. y Mesa-Gresa, P. (2011). Potential benefits and limitations of enriched environments and cognitive activity on age-related behavioural decline. Current Topics in Behavioral Neuroscience, In press. doi:10.1007/7854_2011_134.

Rosenzweig, M. R. (1966). Environmental complexity, cerebral change, and behavior. The American Psychologist, 21, 321-332. doi:10.1037/h0023555

Rueda, A.V., Teixeira, A.M., Yonamine, M., y Camarini, R. (2011).

Environmental enrichment blocks ethanol-induced locomotor sensitization and decreases BDNF levels in the prefrontal cortex in mice. Addiction Biology, In press. doi:10.1111/j.1369-1600.2011.00408.x.

Sale, A., Berardi, N., y Maffei, L. (2009). Enrich the environment to empower the brain. Trends in Neurosciences, 32, 233-239. doi:10.1016/j.tins.2008.12.004.

Schloesser, R. J., Lehmann, M., Martinowich, K., Manji, H. K., y Herkenham, M. (2010). Environmental enrichment requires adult neurogenesis to facilitate the recovery from psychosocial stress.

Molecular Psychiatry, 15, 1152-1163. doi:10.1038/mp.2010.34.

Segovia, G., Del Arco, A., De Blas, M., Garrido, P., y Mora, F. (2010).

Environmental enrichment increases the in vivo extracellular concentration of dopamine in the nucleus accumbens: A microdialysis study. Journal of Neural Transmission (Vienna, Austria: 1996), 117, 1123-1130. doi:10.1007/s00702-010-0447-y.

Smith, M. A., Chisholm, K. A., Bryant, P. A., Greene, J. L., McClean, J. M.,

Stoops, W. W., y Yancey, D. L. (2005). Social and environmental influences on opioid sensitivity in rats: Importance of an opioid’s relative efficacy at the mu-receptor. Psychopharmacology, 181, 27-33.doi:10.1007/s00213-005-2218-2.

Smith, M.A., Bryant, P.A., y McClean, J.M. (2003). Social and environmental enrichment enhances sensitivity to the effects of kappa opioids: studies on antinociception, diuresis and conditioned place preference. Pharmacology, Biochemistry and Behavior, 200, 93-101. doi:10.1016/S0091-3057(03)00189-8.

Smith, M. A., Iordanou, J. C., Cohen, M. B., Cole, K. T., Gergans, S.

R., Lyle, M. A., y Schmidt, K. T. (2009). Effects of environmental enrichment on sensitivity to cocaine in female rats: Importance of control rates of behavior. Behavioural Pharmacology, 20, 312-321.

doi:10.1097/FBP.0b013e32832ec568.

Solinas, M., Thiriet, N., El Rawas, R., Lardeux, V., y Jaber, M. (2009).

Environmental enrichment during early stages of life reduces the behavioral, neurochemical, and molecular effects of cocaine. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 34, 1102-1111. doi:10.1038/npp.2008.51.

Solinas, M., Chauvet, C., Thiriet, N., El Rawas, R., y Jaber, M. (2008).

Reversal of cocaine addiction by environmental enrichment. Proceedings of the National Academy of Sciences of the United States of America, 105, 17145-17150. doi:10.1073/pnas.0806889105.

Solinas, M., Thiriet, N., Chauvet, C., y Jaber, M. (2010). Prevention and

treatment of drug addiction by environmental enrichment. Progress in Neurobiology, 92, 572-592. doi:10.1016/j.pneurobio.2010.08.002.

Stairs, D. J., y Bardo, M. T. (2009). Neurobehavioral effects of environmental enrichment and drug abuse vulnerability. Pharmacology,

Biochemistry, and Behavior, 92, 377-382. doi:10.1016/j.pbb.2009.01.016.

Thiel, K. J., Pentkowski, N. S., Peartree, N. A., Painter, M. R., y Neisewander, J. L. (2010a). Environmental living conditions introduced during forced abstinence alter cocaine-seeking behavior and fos protein expression. Neuroscience, 171, 1187-1196. doi:10.1016/j. neuroscience.2010.10.001.

Thiel, K. J., Engelhardt, B., Hood, L. E., Peartree, N. A., y Neisewander,

J. L. (2010b). The interactive effects of environmental enrichment and extinction interventions in attenuating cue-elicited cocaineseeking behavior in rats. Pharmacology, Biochemistry, and Behavior, 97, 595-602. doi:10.1016/j.pbb.2010.09.014.

Thiriet, N., Amar, L., Toussay, X., Lardeux, V., Ladenheim, B., Becker, K. G., … Jaber, M. (2008). Environmental enrichment during adolescence

regulates gene expression in the striatum of mice. Brain Research, 1222, 31-41. doi:10.1016/j.brainres.2008.05.030.

Thiriet, N., Gennequin, B., Lardeux, V., Chauvet, C., Decressac, M., Janet, T., … Solinas, M. (2011). Environmental enrichment does not reduce the rewarding and neurotoxic effects of methamphetamine. Neurotoxicity Research, 19, 172-182. doi:10.1007/s12640-010-9158-2.

van Praag, H. (2009). Exercise and the brain: Something to chew on. Trends in Neurosciences, 32, 283-290. doi:10.1016/j.tins.2008.12.007.

van Praag, H., Kempermann, G., y Gage, F. H. (2000). Neural consequences of environmental enrichment. Nature Reviews. Neuroscience, 1, 191-198. doi:10.1038/35044558.

Whitaker, J., Moy, S. S., Godfrey, V., Nielsen, J., Bellinger, D., y Bradfield,

J. (2009). Effects of cage size and enrichment on reproductive performance and behavior in C57BL/6Tac mice. Lab Animal, 38, 24-34. doi:10.1038/laban0109-24.

Wong, C.C., Mill, J., y Fernandes, C. (2011). Drugs and addiction: an

introduction to epigenetics. Addiction, 106, 480-489. doi:10.1111/

j.1360-0443.2010.03321.x.

Zhu, J., Bardo, M. T., Green, T. A., Wedlund, P. J., y Dwoskin, L. P. (2007). Nicotine increases dopamine clearance in medial prefrontal cortex in rats raised in an enriched environment. Journal of Neurochemistry, 103, 2575-2588. doi:10.1111/j.1471-4159.2007.04951.x.

Zhu, S. W., Codita, A., Bogdanovic, N., Hjerling-Leffler, J., Ernfors, P.,

Winblad, B., … Mohammed, A. H. (2009). Influence of environmental manipulation on exploratory behaviour in male BDNF knockout mice. Behavioural Brain Research, 197, 339-346. doi:10.1016/j.

bbr.2008.09.032.

Descargas

Publicado

2012-07-01

Número

Vol. 24 Núm. 2 (2012)

Sección

Editorial