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首页> 外文期刊>The European Journal of Neuroscience >Alpha-synuclein in the nucleus accumbens induces changes in cocaine behaviour in rats.
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Alpha-synuclein in the nucleus accumbens induces changes in cocaine behaviour in rats.

机译：伏隔核中的α-突触核蛋白诱导大鼠可卡因行为的改变。

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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.
机译：中脑边缘多巴胺能系统被广泛认为对可卡因奖励和成瘾的神经生物学至关重要。神经蛋白，α-突触核蛋白，是多巴胺能传递中的重要调节剂。它与多巴胺转运蛋白相互作用，并调节多巴胺能神经元的多巴胺能含量，神经传递和突触强度。慢性可卡因滥用者的中脑多巴胺神经元中的α-突触核蛋白水平升高，在经精神刺激剂治疗的动物中其表达增加。 Brenz-Verca等。 （2003）J. Neurosci。，18，1923-1938]。这表明α-突触核蛋白在精神刺激药诱发的行为影响中的作用。为了研究该假设，我们测试了伏伏核（NAcc）中α-突触核蛋白表达的刺激和沉默对大鼠中两种可卡因诱导的行为作用的影响。为此，给动物施用在强力霉素可调节启动子的控制下驱动α-突触核蛋白过表达的慢病毒和/或三种表达靶标特异性siRNA的慢病毒，以沉默α-突触核蛋白mRNA的表达。然后对动物进行可卡因诱导的运动（15mg / kg i.p.）或可卡因诱导的静脉内自我给药（SA; 0.7mg / kg，1小时/天）的测试。 NAcc中α-突触核蛋白的过表达导致运动活性增加了45％，可卡因SA增加了1.9倍，而在同一只动物饲喂强力霉素时，这可以消除。此外，NAcc中α-突触核蛋白的局部抑制导致明显的运动不足活动和SA降低。我们的结果表明，α-突触核蛋白能够调节可卡因诱导的行为影响。这表明靶向α-突触核蛋白功能可以提供可卡因滥用的新治疗策略，目前尚无可用的治疗方法。

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