Journal article

In vivo gene silencing of CD81 by lentiviral expression of small interference RNAs suppresses cocaine-induced behaviour

  • Bahi, Amine Biochemistry, Department of Medicine, Fribourg, Switzerland
  • Boyer, Frederic Biochemistry, Department of Medicine, Fribourg, Switzerland
  • Kolira, Manoj Biochemistry, Department of Medicine, Fribourg, Switzerland
  • Dreyer, Jean-Luc Biochemistry, Department of Medicine, Fribourg, Switzerland
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Published in:
  • Journal of Neurochemistry. - 2005, vol. 92(5), no. 1243
English The tetraspanin CD81 is induced in the mesolimbic dopaminergic pathway after cocaine administration. To further investigate its role, a regulatable lentivirus (Lenti-CD81) bearing the CD81 gene under the control of a tetracycline-inducible promoter and lentiviruses expressing short hairpin RNA (shRNA) targeted against CD81 (Lenti-CD81-shRNAs) have been prepared. Infection of HEK293T cells in vitro with Lenti-CD81-shRNAs resulted in 96.5% gene silencing (from quantitative real-time PCR(qRT-PCR) and immunocytochemistry). In vivo delivery of Lenti-CD81-shRNA into the nucleus accumbens or ventral tegmental area resulted in 91.3 and 94% silencing of endogenous CD81, respectively. Stereotaxic injection of Lenti-CD81 into these regions, resulting in CD81 overexpression, induced a four- to fivefold increase in locomotor activity after chronic cocaine administration, which returned to basal levels when Lenti-CD81-shRNA had been coinjected or when CD81 expression was blocked by doxycycline. Furthermore, silencing endogenous CD81 in vivo resulted in a significant decrease in locomotor activity over controls, again suppressing cocaine-induced behaviour.
Faculté des sciences et de médecine
Département de Médecine
  • English
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