Boyer, Frederic Dreyer, Jean-Luc 2007-11-13 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 <i>et al</i>. (2003) <i>J. Neurosci</i>., 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. application/pdf https://folia.unifr.ch/global/documents/300711 https://folia.unifr.ch/documents/300711/files/dreyer_asn.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1111/j.1460-9568.2007.05878.x info:eu-repo/semantics/openAccess License undefined European Journal of Neuroscience. - 2007, vol. 26, no. 10, p. 2764-2776 addiction drugs of abuse in vivo gene transfer lentivirus plasticity siRNA info:eu-repo/classification/udc/57 Alpha-synuclein in the nucleus accumbens induces changes in cocaine behaviour in rats http://purl.org/coar/resource_type/c_6501