Cdk5抑制剂β-丁内酯损害大鼠基底外侧杏仁核海洛因相关记忆的再巩固,Addiction Biology

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Cdk5抑制剂β-丁内酯损害大鼠基底外侧杏仁核海洛因相关记忆的再巩固
Addiction Biology ( IF 3.1 ) Pub Date : 2023-08-18 , DOI: 10.1111/adb.13326
Haoyu Li _{1,

2,

3} , Haiting Zhao _{3,

4} , Ting Hu _{1,

2,

3} , Li Meng _{1,

2,

3} , Xin Mo _{3,

5} , Mengqi Gong _{1,

2,

3} , Yiwei Liao _{1,

2,

3}

Affiliation

与海洛因相关的适应不良记忆的持续存在是由与药物相关的刺激触发的，这些刺激提醒个体药物的令人愉悦和有益的作用，可能会阻碍戒毒努力。细胞周期蛋白依赖性激酶 5 (Cdk5) 是一种神经元丝氨酸/苏氨酸蛋白激酶，在多种神经元功能中发挥作用，已被证明与药物成瘾以及学习和记忆有关。在这里，我们的目的是使用自我给药大鼠模型来研究基底外侧杏仁核 (BLA) 中的 cdk5 活性在海洛因寻求复发中的作用。雄性大鼠接受了为期 10 天的海洛因自我注射训练，在此期间，主动戳鼻子会导致海洛因静脉输注，并伴有提示。然后，老鼠经历了为期 10 天的鼻子戳灭绝，随后进行了海洛因寻求行为测试。我们发现，BLA 内输注 β-丁内酯（100 ng/侧）（一种 Cdk5 抑制剂），在重新激活后 5 分钟给药，可导致海洛因寻求行为随后减少。进一步的实验表明，β-丁内酯的作用取决于重新激活的记忆、时间特异性和海洛因相关记忆复发的持久性。结果提供了提示性证据，表明 BLA 中 Cdk5 的活性对于海洛因相关记忆至关重要，并且特定抑制剂 β-丁内酯可能具有作为治疗海洛因滥用的物质的潜力。

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The Cdk5 inhibitor β-butyrolactone impairs reconsolidation of heroin-associated memory in the rat basolateral amygdala

The persistence of maladaptive heroin-associated memory, which is triggered by drug-related stimuli that remind the individual of the drug's pleasurable and rewarding effects, can impede abstinence efforts. Cyclin-dependent kinase 5 (Cdk5), a neuronal serine/threonine protein kinase that plays a role in multiple neuronal functions, has been demonstrated to be involved in drug addiction and learning and memory. Here, we aimed to investigate the role of cdk5 activity in the basolateral amygdala (BLA) in relapse to heroin seeking, using a self-administration rat model. Male rats underwent 10 days of heroin self-administration training, during which an active nose poke resulted in an intravenous infusion of heroin that was accompanied by a cue. The rats then underwent nose poke extinction for 10 days, followed by subsequent tests of heroin-seeking behaviour. We found that intra-BLA infusion of β-butyrolactone (100 ng/side), a Cdk5 inhibitor, administered 5 min after reactivation, led to a subsequent decrease in heroin-seeking behaviour. Further experiments demonstrated that the effects of β-butyrolactone are dependent on reactivated memories, temporal-specific and long-lasting on relapse of heroin-associated memory. Results provide suggestive evidence that the activity of Cdk5 in BLA is critical for heroin-associated memory and that the specific inhibitor, β-butyrolactone, may hold potential as a substance for the treatment of heroin abuse.

更新日期：2023-08-19

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