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首页> 外文期刊>Journal of Molecular Psychiatry >mGluR2/3 blockade produces rapid and long-lasting reversal of anhedonia caused by chronic stress exposure
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mGluR2/3 blockade produces rapid and long-lasting reversal of anhedonia caused by chronic stress exposure

机译：mGluR2 / 3阻断可导致长期压力暴露引起的快感和快感的逆转

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BackgroundDepression is a prevalent neuropsychiatric disorder that affects an estimated 350 million people worldwide. Currently available treatments for depression are lacking in both speed of onset and efficacy. Recent pharmacological efforts have targeted the glutamatergic neurotransmitter system using the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine to produce rapid and robust antidepressant effects, however the widespread clinical use of ketamine is limited due to side effects and abuse liability. More recently, work evaluating metabotropic mGluR2/3 receptor antagonists has demonstrated many similarities with ketamine. MethodsMale, Sprague–Dawley rats were exposed to a chronic unpredictable stress paradigm, which produces decreased sucrose preference, a measure of anhedonia. Rats were then treated with vehicle or a single injection of the mGluR2/3 antagonist LY341495 (3?mg/kg, i.p.) and tested at 24?hrs, 48?hrs or 10?days after a single treatment. ResultsWe demonstrate that a single treatment with LY341495 produces a rapid (within 1–2?days) and long-lasting (10?days) reversal of anhedonia caused by chronic unpredictable stress in rats. This model provides a rigorous test of rapid-acting agents as typical antidepressants require several weeks of treatment to produce a response. ConclusionsThese data suggest that LY341495 has the ability to produce rapid and robust antidepressant effects similar to ketamine. Together, the results highlight the potential for similar compounds to produce rapid and lasting efficacy for the treatment of depression.
机译：背景技术抑郁症是一种普遍存在的神经精神疾病，估计会影响全球3.5亿人。目前可用的抑郁症治疗方法既缺乏发作速度，又缺乏疗效。最近的药理努力已经针对使用N-甲基-D-天冬氨酸（NMDA）受体拮抗剂氯胺酮的谷氨酸能神经递质系统产生了快速而稳定的抗抑郁作用，但是由于副作用和滥用的原因，氯胺酮的广泛临床应用受到了限制。最近，评估代谢型mGluR2 / 3受体拮抗剂的工作证明与氯胺酮有许多相似之处。方法：雄性Sprague–Dawley大鼠暴露于慢性不可预知的压力范式，这会降低蔗糖的偏爱，这是一种对快感不足的量度。然后用赋形剂或单次注射mGluR2 / 3拮抗剂LY341495（3？mg / kg，腹腔注射）治疗大鼠，并在单次治疗后24小时，48小时或10天进行测试。结果我们证明，单用LY341495治疗可导致大鼠慢性不可预测的压力引起的快感（在1-2天之内）和持久的（10天）逆转。该模型提供了对速效剂的严格测试，因为典型的抗抑郁药需要数周的治疗才能产生反应。结论这些数据表明，LY341495具有产生与氯胺酮相似的快速而强大的抗抑郁作用的能力。总之，这些结果凸显了类似化合物在产生快速而持久的抑郁症治疗功效方面的潜力。

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