Neuroplasticity of the extended amygdala in opioid withdrawal and prolonged opioid abstinence.
Neuroplasticity of the extended amygdala in opioid withdrawal and prolonged opioid abstinence.
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DOI：
10.3389/fphar.2023.1253736
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发表时间：
2023
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
阿片类药物使用障碍的特征是过度使用阿片类药物、无法控制其使用、停用阿片类药物后出现戒断综合征以及长期复发的可能性。阿片类药物成瘾的行为阶段与表征对手过程动机观的情感体验相对应。在这个框架中，积极参与伴随着积极的情感体验，从而产生“奖励渴望”，而反对过程，即节制，则与产生“救济渴望”的消极情感体验相关。缓解渴望伴随着对阿片类药物戒断期间戒断的负面强化方面的超敏反应而发展。假设这些负面情感体验源于对称为“扩展杏仁核”的情感处理网络的神经适应。这个负价网络包括杏仁核中央核（CeA）、终纹床核（BNST）和伏隔核壳（NAc壳）三个核心结构，以及来自基底外侧杏仁核（BLA）的主要输入。为了更好地了解该系统的主要组成部分，我们回顾了它们的功能、输入和输出，以及阿片类药物戒断动物模型中相关的神经可塑性。这些模型展示了阿片类药物戒断和戒断的躯体、动机、情感和学习相关模型。这些压力和动机系统中的神经适应伴随着消极的情感和厌恶的经历，通常会导致旧病复发。 CeA 神经可塑性通过谷氨酸可塑性和含有促肾上腺皮质激素释放因子 (CRF) 的神经元的变化解释了阿片类药物戒断所产生的许多厌恶和恐惧相关的影响。 BNST 突触前和突触后含 GABA 神经元的神经适应及其去甲肾上腺素能调节可能是造成各种厌恶情感体验和适应不良行为的原因。阿片类药物戒断会产生多巴胺能低下和无动机状态，并导致 NAc 壳兴奋性的神经适应性增加，这两者都与复发的可能性增加有关。最后，BLA 向海马和皮质区域的传输会影响高级执行系统对阿片类药物戒断条件性厌恶效应的感知。在阿片类药物戒断过程中，预防或逆转杏仁核中这些不同的神经适应可能会为这种危及生命的疾病带来有希望的新干预措施。
Opioid use disorder is characterized by excessive use of opioids, inability to control its use, a withdrawal syndrome upon discontinuation of opioids, and long-term likelihood of relapse. The behavioral stages of opioid addiction correspond with affective experiences that characterize the opponent process view of motivation. In this framework, active involvement is accompanied by positive affective experiences which gives rise to “reward craving,” whereas the opponent process, abstinence, is associated with the negative affective experiences that produce “relief craving.” Relief craving develops along with a hypersensitization to the negatively reinforcing aspects of withdrawal during abstinence from opioids. These negative affective experiences are hypothesized to stem from neuroadaptations to a network of affective processing called the “extended amygdala.” This negative valence network includes the three core structures of the central nucleus of the amygdala (CeA), the bed nucleus of the stria terminalis (BNST), and the nucleus accumbens shell (NAc shell), in addition to major inputs from the basolateral amygdala (BLA). To better understand the major components of this system, we have reviewed their functions, inputs and outputs, along with the associated neural plasticity in animal models of opioid withdrawal. These models demonstrate the somatic, motivational, affective, and learning related models of opioid withdrawal and abstinence. Neuroadaptations in these stress and motivational systems are accompanied by negative affective and aversive experiences that commonly give rise to relapse. CeA neuroplasticity accounts for many of the aversive and fear-related effects of opioid withdrawal via glutamatergic plasticity and changes to corticotrophin-releasing factor (CRF)-containing neurons. Neuroadaptations in BNST pre-and post-synaptic GABA-containing neurons, as well as their noradrenergic modulation, may be responsible for a variety of aversive affective experiences and maladaptive behaviors. Opioid withdrawal yields a hypodopaminergic and amotivational state and results in neuroadaptive increases in excitability of the NAc shell, both of which are associated with increased vulnerability to relapse. Finally, BLA transmission to hippocampal and cortical regions impacts the perception of conditioned aversive effects of opioid withdrawal by higher executive systems. The prevention or reversal of these varied neuroadaptations in the extended amygdala during opioid withdrawal could lead to promising new interventions for this life-threatening condition.
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影响因子：
4.3
作者：
Koob GF
通讯作者：
Koob GF
影响因子：
5.3
作者：
Dumont, ÉC;Williams, JT
通讯作者：
Williams, JT
DOI：
10.1016/j.pnpbp.2021.110435
发表时间：
2021-09-20
影响因子：
5.6
作者：
Baidoo, Nana;Leri, Francesco
通讯作者：
Leri, Francesco
影响因子：
5.3
作者：
Chater TE;Goda Y
通讯作者：
Goda Y
影响因子：
3.4
作者：
Alvarez-Bagnarol, Yocasta;Marchette, Renata C. N.;Vendruscolo, Leandro F.
通讯作者：
Vendruscolo, Leandro F.