Uridine decreases morphine-induced behavioral sensitization by decreasing dorsal striatal dopamine release possibly via agonistic effects at GABA(A) receptors
Uridine decreases morphine-induced behavioral sensitization by decreasing dorsal striatal dopamine release possibly via agonistic effects at GABA(A) receptors
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尿苷可能通过 GABA(A) 受体的激动作用减少背侧纹状体多巴胺的释放，从而降低吗啡诱导的行为敏感性
DOI：
10.1016/j.euroneuro.2014.06.010
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发表时间：
2014
影响因子：
5.6
通讯作者：
Yang Jingyu
中科院分区：
文献类型：
--
作者：
Liu Ping;Wu Chunfu;Song Wu;Yu Lisha;Yang Xiaofeng;Xiang Rongwu;Wang Fang;Yang Jingyu
尿苷是一种潜在的内源性神经调质，与多巴胺能系统相互作用，调节多巴胺相关行为。本研究探讨了尿苷对吗啡诱导的小鼠多动和行为敏化的影响以及对多巴胺能神经传递的调节作用，这可能有助于了解尿苷及其代谢产物如何作为GABA A受体的调节剂。结果表明，无论是全身（30或100毫克/公斤）或中央（30，100或300纳米）尿苷给药显着减弱小鼠急性吗啡治疗诱导的活动过度。脑室注射尿嘧啶和β-丙氨酸也能抑制吗啡诱导的多动症。尿苷，一种已知的GABA受体调节剂，增加了脑中GABA的细胞外水平。此外，GABA A受体拮抗剂荷包牡丹碱显着减弱尿苷对吗啡诱导的活动过度的影响，表明GABA A受体可能介导尿苷及其代谢产物对吗啡相关活动的影响。在体微透析实验表明，尿苷可逆转吗啡致敏小鼠背侧纹状体多巴胺的释放。总之，这些数据表明，尿苷及其代谢产物对吗啡诱导的多动症和建立的行为敏化的治疗作用可能部分介导的干扰多巴胺能系统可能通过激动剂作用于GABAA受体。
Uridine, a potential endogenous neuromodulator, has been demonstrated to interact with the dopaminergic system and to regulate dopamine-related behaviors. The present study investigated the effects of uridine on morphine-induced hyperactivity and behavioral sensitization and on modulating dopaminergic neurotransmission in mice, which may help to understand how uridine and its metabolites act as modulators of the GABAAreceptors. The results showed that either systemic (30 or 100 mg/kg) or central (30, 100 or 300 nM) uridine administration significantly attenuated the hyperactivity induced by acute morphine treatment in mice. Intracerebroventricular administration of uracil and β-alanine also inhibited morphine-induced hyperactivity. Uridine, a known modulator of the GABA receptors, increased the extracellular levels of GABA in the brain. In addition, the GABAAreceptors antagonist bicuculline significantly attenuated the effects of uridine on morphine-induced hyperactivity, suggesting that the GABAAreceptors potentially mediate the effects of uridine and its metabolites on morphine-related activity. It was also observed that morphine-induced locomotor sensitization was abolished after chronic uridine treatment.In vivomicrodialysis demonstrated that uridine reversed morphine-induced dopamine release in the dorsal striatum of morphine-sensitized mice. In conclusion, these data suggest that the therapeutic effects of uridine and its metabolites on morphine-induced hyperactivity and established behavioral sensitization may be mediated in part by interfering with the dopaminergic system possibly via agonistic effects at GABAAreceptors.