Journal article

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
Published in:
  • European Journal of Neuroscience. - 2007, vol. 26, no. 10, p. 2764-2776
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.
Faculté des sciences et de médecine
Département de Médecine
  • English
Biological sciences
License undefined
Persistent URL

Document views: 54 File downloads:
  • dreyer_asn.pdf: 89