RGD Reference Report - Alpha-synuclein in the nucleus accumbens induces changes in cocaine behaviour in rats. - Rat Genome Database

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

Authors: Boyer, F  Dreyer, JL 
Citation: Boyer F and Dreyer JL, Eur J Neurosci. 2007 Nov;26(10):2764-76.
RGD ID: 2291826
Pubmed: PMID:18001274   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1460-9568.2007.05878.x   (Journal Full-text)

The mesolimbic dopaminergic system is widely recognized to be critical to the neurobiology of cocaine reward and addiction. The neuronal protein, alpha-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 alpha-synuclein in psychostimulant-induced behavioural effects. To investigate this hypothesis, we tested the effect of stimulation and silencing of alpha-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 alpha-synuclein overexpression under the control of a doxycycline regulatable promoter and/or with three lentiviruses expressing target-specific siRNAs, aimed at silencing alpha-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 alpha-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 alpha-synuclein in the NAcc resulted in significant hypolocomotion activity and a decrease in SA. Our results demonstrate that alpha-synuclein is able to modulate cocaine-induced behavioural effects. This suggests that targeting alpha-synuclein function could provide new therapeutic strategies to treat cocaine abuse, for which there is no available treatment.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SncaRatbehavioral response to cocaine  IMP  RGD 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SncaRatsynaptic vesicle  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Snca  (synuclein alpha)


Additional Information