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Stress-induced cross-sensitization to amphetamine is related to changes in the dopaminergic system

  • Basic Neurosciences, Genetics and Immunology - Original Article
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Abstract

Repeated stress engenders behavioral sensitization. The mesolimbic dopamine system is critically involved in drug-induced behavioral sensitization. In the present study we examined the differences between adolescent and adult rats in stress-induced behavioral sensitization to amphetamine and changes in dopamine (DA) and its metabolite levels in the mesolimbic system. Adolescent or adult rats were restrained for 2 h, once a day, for 7 days. Three days after the last exposure to stress, the animals were challenged with saline or amphetamine (1.0 mg/kg i.p.) and amphetamine-induced locomotion was recorded for 40 min. Immediately after the behavioral tests, rats were decapitated and the nucleus accumbens (NAcc), ventral tegmental area (VTA) and amygdala (AM) were removed to measure tissue levels of DA and its metabolites by HPLC. Exposure to repeated restraint stress promoted behavioral sensitization to amphetamine in both adult and adolescent rats. In adult rats, amphetamine administration increased DA levels in both the stress and control groups in the NAcc and VTA. In adolescent rats, amphetamine increased DA levels in the NAcc in rats exposed to stress. Furthermore, in the AM of adolescent rats in the control group, amphetamine increased the DA levels; however, amphetamine reduced this neurotransmitter in the rats that were exposed to stress. No alteration was observed in the dopamine metabolite levels. Therefore, stress promoted behavioral sensitization to amphetamine and this may be related to changes in DA levels in the mesolimbic system. These changes appear to be dependent on ontogeny.

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Acknowledgments

The authors appreciate the excellent technical assistance by Elisabete Z.P. Lepera, Francisco Rocateli and Rosana F.P. Silva. This work was supported by Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP-2007/08087-7).

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Authors and Affiliations

  1. Laboratory of Pharmacology, School of Pharmaceutical Sciences, São Paulo State University-UNESP, Rod. Araraquara-Jaú Km 1, Araraquara, São Paulo, 14801-902, Brazil

    Fábio C. Cruz, Marcelo Tadeu Marin, Rodrigo Molini Leão & Cleopatra S. Planeta

  2. Interinstitutional Graduate Program in Physiological Sciences, Federal University of São Carlos, Rod. Washington Luiz, Km 235, São Carlos, São Paulo, Brazil

    Rodrigo Molini Leão & Cleopatra S. Planeta

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  1. Fábio C. Cruz
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  2. Marcelo Tadeu Marin
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  3. Rodrigo Molini Leão
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  4. Cleopatra S. Planeta
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Correspondence to Cleopatra S. Planeta.

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Cruz, F.C., Marin, M.T., Leão, R.M. et al. Stress-induced cross-sensitization to amphetamine is related to changes in the dopaminergic system. J Neural Transm 119, 415–424 (2012). https://doi.org/10.1007/s00702-011-0720-8

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  • DOI: https://doi.org/10.1007/s00702-011-0720-8

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