RT Journal Article SR Electronic T1 Enriched Environment Confers Resistance to 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine and Cocaine: Involvement of Dopamine Transporter and Trophic Factors JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 10999 OP 11007 DO 10.1523/JNEUROSCI.23-35-10999.2003 VO 23 IS 35 A1 Bezard, Erwan A1 Dovero, Sandra A1 Belin, David A1 Duconger, Sophie A1 Jackson-Lewis, Vernice A1 Przedborski, Serge A1 Piazza, Pier Vincenzo A1 Gross, Christian E. A1 Jaber, Mohamed YR 2003 UL http://www.jneurosci.org/content/23/35/10999.abstract AB 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.