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Alpha-synuclein in the nucleus accumbens induces changes in cocaine behaviour in rats

  • Boyer, Frederic Institute of Biochemistry, University of Fribourg, Switzerland
  • Dreyer, Jean-Luc Institute of Biochemistry, University of Fribourg, Switzerland
    13.11.2007
Published in:
  • European Journal of Neuroscience. - 2007, vol. 26, no. 10, p. 2764-2776
addiction
drugs of abuse
in vivo gene transfer
lentivirus
plasticity
siRNA
English The mesolimbic dopaminergic system is widely recognized to be critical to the neurobiology of cocaine reward and addiction. The neuronal protein, α-synuclein, is an important regulator in dopaminergic transmission. It interacts with the dopamine transporter, and regulates dopaminergic content, neurotransmission and synaptic strength of dopaminergic neurons. Alpha-synuclein levels are elevated in midbrain dopamine neurons of chronic cocaine abusers, and its expression is increased in psychostimulant-treated animals [M.S. Brenz-Verca et al. (2003) J. Neurosci., 18, 1923–1938]. This suggests a role for α-synuclein in psychostimulant-induced behavioural effects. To investigate this hypothesis, we tested the effect of stimulation and silencing of α-synuclein expression in the nucleus accumbens (NAcc) on two cocaine-induced behavioural effects in the rat. For this purpose, animals were administered with lentiviruses driving α-synuclein overexpression under the control of a doxycycline regulatable promoter and/or with three lentiviruses expressing target-specific siRNAs, aimed at silencing α-synuclein mRNA expression. Animals were then tested for cocaine-induced locomotion (15 mg/kg i.p.) or cocaine-induced intravenous self-administration (SA; 0.7 mg/kg, 1 h/day). Overexpression of α-synuclein in the NAcc induced a 45% increase in locomotor activity and a 1.9-fold increase of cocaine SA, which could be abolished when the same animal was fed doxycycline. Furthermore, local inhibition of α-synuclein in the NAcc resulted in significant hypolocomotion activity and a decrease in SA. Our results demonstrate that α-synuclein is able to modulate cocaine-induced behavioural effects. This suggests that targeting α-synuclein function could provide new therapeutic strategies to treat cocaine abuse, for which there is no available treatment.
Faculty
Faculté des sciences et de médecine
Department
Département de Médecine
Language
  • English
Classification
Biological sciences
License
License undefined
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Persistent URL
https://folia.unifr.ch/unifr/documents/300711
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