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Published on: September 16, 2015
A decrease in gamma-synuclein expression within the nucleus accumbens increases cocaine intravenous
Frédéric Boyer1, Eric Balado, Pier V Piazza
1Institute of Biochemistry, University of Fribourg, Switzerland.
Abstract:
Except as a marker of cancer progression, gamma-synuclein (GSyn) had received little attention. Recent data showed however that GSyn modulates cocaine-induced locomotor effects, suggesting that it could also play a role in cocaine reinforcing effects. In the rat, siRNAs targeting GSyn expression were injected in the nucleus accumbens and cocaine reinforcing effects were evaluated by means of intravenous self-administration. A dose-response curve was followed by procedures of progressive ratio, extinction, cocaine- and cue-induced reinstatements. Decrease of GSyn expression increased self-administration over a large range of doses. This effect was associated with an increase in cocaine-induced reinstatement. The present data reveal that GSyn exert a specific negative control on cocaine-induced reinforcing and incentive effects.
Insights
Gamma-synuclein (GSyn) negatively controls cocaine reinforcement. Reducing GSyn levels in rats increased cocaine self-administration and reinstatement, revealing its role in addiction.
Area of Science:
- Neuroscience
- Molecular Biology
- Addiction Research
Background:
- Gamma-synuclein (GSyn) is primarily known as a cancer progression marker.
- Emerging evidence suggests GSyn influences locomotor activity modulated by cocaine.
- This indicates a potential role for GSyn in the reinforcing effects of cocaine.
Purpose of the Study:
- To investigate the role of gamma-synuclein (GSyn) in modulating the reinforcing and incentive effects of cocaine.
- To determine if GSyn expression levels impact cocaine self-administration and reinstatement behaviors.
Main Methods:
- Rats received siRNA injections targeting GSyn expression in the nucleus accumbens.
- Cocaine reinforcing effects were assessed using intravenous self-administration.
- Evaluations included dose-response curves, progressive ratio, extinction, and cocaine/cue-induced reinstatement.
Main Results:
- Decreased GSyn expression significantly increased cocaine self-administration across various doses.
- Reduced GSyn levels were associated with heightened cocaine-induced reinstatement of drug-seeking behavior.
- These findings highlight GSyn's specific inhibitory influence on cocaine's effects.
Conclusions:
- Gamma-synuclein (GSyn) exerts specific negative control over the reinforcing and incentive properties of cocaine.
- Modulating GSyn expression offers a potential therapeutic avenue for cocaine addiction.
- GSyn represents a novel target for understanding and treating substance use disorders.
