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首页> 外文期刊>Addiction biology >Lysophosphatidic acid‐induced increase in adult hippocampal neurogenesis facilitates the forgetting of cocaine‐contextual memory
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Lysophosphatidic acid‐induced increase in adult hippocampal neurogenesis facilitates the forgetting of cocaine‐contextual memory

机译：成年海马神经发生的溶血磷脂酸诱导促进了可卡因语境记忆的遗忘

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Abstract Erasing memories of cocaine–stimuli associations might have important clinical implications for addiction therapy. Stimulating hippocampal plasticity by enhancing adult hippocampal neurogenesis (AHN) is a promising strategy because the addition of new neurons may not only facilitate new learning but also modify previous connections and weaken retrograde memories. To investigate whether increasing AHN prompted the forgetting of previous contextual cocaine associations, mice trained in a cocaine‐induced conditioned place preference (CPP) paradigm were administered chronic intracerebroventricular infusions of lysophosphatidic acid (LPA, an endogenous lysophospholipid with pro‐neurogenic actions), ki16425 (an LPA 1/3 receptor antagonist) or a vehicle solution, and they were tested 23?days later for CPP retention and extinction. The results of immunohistochemical experiments showed that the LPA‐treated mice exhibited reduced long‐term CPP retention and an approximately twofold increase in the number of adult‐born hippocampal cells that differentiated into mature neurons. Importantly, mediation analyses confirmed a causal role of AHN in reducing CPP maintenance. In contrast, the ki16425‐treated mice displayed aberrant responses, with initially decreased CPP retention that progressively increased across the extinction sessions, leading to no effect on AHN. The pharmacological treatments did not affect locomotion or general exploratory or anxiety‐like responses. In a second experiment, normal and LPA 1 ‐receptor‐deficient mice were acutely infused with LPA, which revealed that LPA 1 ‐mediated signaling was required for LPA‐induced proliferative actions. These results suggest that the LPA/LPA 1 pathway acts as a potent in vivo modulator of AHN and highlight the potential usefulness of pro‐AHN strategies to treat aberrant cognition in those addicted to cocaine.
机译：摘要可卡因刺激协会的回忆可能对成瘾治疗具有重要的临床意义。通过增强成人海马神经发生（AHN）刺激海马塑性是一个有希望的策略，因为添加新的神经元可能不仅可以促进新的学习，而且还可以改变以前的联系并削弱逆行回忆。为了探讨越来越多的Ahn促使遗忘前的上下文可卡因关联，培训在可卡因诱导的条件偏好（CPP）范式中培训的小鼠慢性脑脊液的镝磷脂酸（LPA，内源性溶血磷脂，具有亲神经源性作用），Ki16425 （LPA 1/3受体拮抗剂）或载体溶液，并在23℃下进行测试，用于CPP保留和消灭。免疫组织化学实验结果表明，LPA处理的小鼠表现出降低的长期CPP保留，并且在分化为成熟神经元的成人出生的海马细胞数量的大致两倍增加。重要的是，中介分析证实了AHN在降低CPP维护方面的因果作用。相反，Ki16425治疗的小鼠呈现异常反应，最初降低了逐步增加了消光会话的CPP保留，导致对AHN没有影响。药理治疗不影响运动或普通探索性或焦虑的反应。在第二种实验中，正常和LPA 1 - 缺乏小鼠急性地注入LPA，这揭示了LPA诱导的增殖作用所需的LPA 1介导的信号传导。这些结果表明，LPA / LPA 1途径作为AHN的体内调节剂的效力，并突出了Pro-Ahn策略在沉迷于可卡因的那些对异常认知的潜在有用性。

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