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The Journal of Neuroscience, December 3, 2003, 23(35):10999-11007

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Development/Plasticity/Repair
Enriched Environment Confers Resistance to 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine and Cocaine: Involvement of Dopamine Transporter and Trophic Factors

Erwan Bezard,¹ Sandra Dovero,¹ David Belin,² Sophie Duconger,² Vernice Jackson-Lewis,³ Serge Przedborski,³ Pier Vincenzo Piazza,² Christian E. Gross,¹ and Mohamed Jaber⁴

¹Basal Gang, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 5543, Université Victor Segalen, 33076 Bordeaux Cedex, France, ²Institut National de la Santé et de la Recherche Médicale 259, Institut François Magendie, 33077 Bordeaux Cedex, France, ³Departments of Neurology and Pathology, Columbia University, New York, New York 10032, and ⁴CNRS UMR 6558, Université de Poitiers, 86022 Poitiers Cedex, France

We investigated, in mice, the influence of life experience on the vulnerability to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a major neurotoxin that induces a Parkinson's disease-like syndrome in humans, and to cocaine, a potent psychostimulant that promotes drug addiction. Our findings show that adult C57BL/6 mice raised in an enriched environment (EE) for only 2 months are significantly more resistant to both drugs compared with mice raised in a standard environment (SE). Indeed, EE mice showed decreased locomotor activity in response to cocaine (10 and 20 mg/kg) as well as a different pattern of c-fos expression in the striatum compared with SE mice. After MPTP treatment, SE mice showed a 75% loss of dopamine neurons, whereas EE mice showed only a 40% loss. The dopamine transporter plays a key role in mediating the effects of both drugs. We thus investigated the regulation of its expression. EE mice showed less dopamine transporter binding in the striatum and less dopamine transporter mRNA per dopamine neuron at the cellular level as demonstrated by in situ hybridization. In addition, enriched environment promoted an increase in the expression of brain-derived neurotrophic factor in the striatum. These data provide a direct demonstration of the beneficial consequences that a positive environment has in preventing neurodegeneration and in decreasing responsiveness to cocaine. Furthermore, they suggest that the probability of developing neurological disorders such as Parkinson's disease or vulnerability to psychostimulants may be related to life experience.

Key words: environmental enrichment; tyrosine hydroxylase; c-fos; dopamine transporter; BDNF; Parkinson's disease; drug of abuse

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Received May 30, 2003; revised September 4, 2003; accepted October 1, 2003.

This article has been cited by other articles:

				M. Solinas, C. Chauvet, N. Thiriet, R. El Rawas, and M. Jaber From the Cover: Reversal of cocaine addiction by environmental enrichment PNAS, November 4, 2008; 105(44): 17145 - 17150. [Abstract] [Full Text] [PDF]

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				G. M. Petzinger, J. P. Walsh, G. Akopian, E. Hogg, A. Abernathy, P. Arevalo, P. Turnquist, M. Vuckovic, B. E. Fisher, D. M. Togasaki, et al. Effects of Treadmill Exercise on Dopaminergic Transmission in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Lesioned Mouse Model of Basal Ganglia Injury J. Neurosci., May 16, 2007; 27(20): 5291 - 5300. [Abstract] [Full Text] [PDF]

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