Journal article

The role of gamma-synuclein in cocaine-induced behaviour in rats

  • Boyer, Frederic Institute of Biochemistry, University of Fribourg, Switzerland
  • Dreyer, Jean-Luc Institute of Biochemistry, University of Fribourg, Switzerland
Published in:
  • European Journal of Neuroscience. - 2008, vol. 27, no. 11, p. 2938 - 2951
English The aim of this study was to investigate the role of γ-synuclein in the rewarding effects of chronic cocaine administration and its putative interaction with the dopamine transporter (DAT). For this purpose, regulatable lentiviruses driving overexpression of the rat γ-synuclein or DAT have been prepared, as well as lentiviruses expressing siRNAs, aimed at silencing either DAT or γ-synuclein mRNA expression. Overexpression of DAT in the nucleus accumbens (NAc) induced a 35% decrease in locomotor activity, which could be abolished when the same animal was fed doxycycline. Furthermore, local inhibition of DAT in the NAc, using lentiviruses expressing siRNAs targeted against DAT, resulted in significant hyperlocomotion activity (72% increase over controls). By contrast, overexpression of γ-synuclein in the NAc alone had no effect, while local silencing lead to a significant decrease in cocaine-induced locomotor activity (47% decrease compared with controls). Surprisingly, coinjection lentiviruses expressing DAT and γ-synuclein − leading to overexpression of both proteins in the NAc − resulted in a strong increase in cocaine-induced rat locomotor activity (52% increase compared with controls), which was abolished upon locally silencing these genes, suggesting a synergetic role of both proteins, possibly mediated through a direct interaction.
Faculté des sciences et de médecine
Département de Médecine
  • English
Biological sciences
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