Adult neurogenesis in the dentate gyrus (DG) is strongly influenced by drug-taking behavior and may have a role in the etiology of drug-seeking behavior. However, mechanistic studies on the relationship of neurogenesis on drug seeking are limited. Outbred Wistar rats experienced extended access methamphetamine self-administration and individual differences in drug taking defined animals with higher preferred and lower preferred levels of drug intake. Forced abstinence from higher preferred levels of drug taking enhanced neurogenesis and neuronal activation of granule cell neurons (GCNs) in the DG and produced compulsive-like drug reinstatement. Systemic treatment with the drug Isoxazole-9 (a synthetic small molecule known to modulate neurogenesis in the adult rodent brain) during abstinence blocked compulsive-like context-driven methamphetamine reinstatement. Isoxazole-9 modulated neurogenesis, neuronal activation and structural plasticity of GCNs, and expression of synaptic proteins associated with learning and memory in the DG. These findings identify a subset of newly born GCNs within the DG that could directly contribute to drug-seeking behavior. Taken together, these results support a direct role for the importance of adult neurogenesis during abstinence in compulsive-like drug reinstatement.

中文翻译：

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合成的小分子异恶唑9可以防止甲基苯丙胺复发。

齿状回（DG）中的成年神经发生受到吸毒行为的强烈影响，并且可能在寻找毒品行为的病因中起作用。然而，关于神经发生与药物寻找关系的机理研究是有限的。远距离Wistar大鼠经历了甲基苯丙胺的自我扩展服用和药物定义个体的药物摄入个体差异，其较高和较低的药物摄入水平。在DG中优先采取更高的药物强制禁欲措施，以增强DG中的神经元生成和颗粒细胞神经元（GCN）的神经元活化，并恢复强迫性药物。禁欲期间用药物Isoxazole-9（一种合成的小分子，已知能调节成年啮齿动物神经发生的合成小分子）的全身治疗会阻止强迫性情境驱动的甲基苯丙胺恢复。异恶唑9调节DG的神经发生，神经元激活和GCN的结构可塑性，以及与学习和记忆相关的突触蛋白的表达。这些发现确定了DG中新出生的GCN的子集，这些子集可能直接有助于寻求药物的行为。综上所述，这些结果支持禁欲期间成人神经再生在强迫性药物恢复中的重要性的直接作用。这些发现确定了DG中新出生的GCN的子集，这些子集可能直接有助于寻求药物的行为。综上所述，这些结果直接证明了禁欲期间成人神经再生在强迫性药物恢复中的重要性。这些发现确定了DG中新出生的GCN的子集，这些子集可能直接有助于寻求药物的行为。综上所述，这些结果支持禁欲期间成人神经再生在强迫性药物恢复中的重要性的直接作用。