Opioids are powerful drugs that usurp and overpower the reward function of endogenous opioids and engage dramatic tolerance and withdrawal via molecular and neurocircuitry neuroadaptations within the same reward system. However, they also engage the brain systems for stress and pain (somatic and emotional) while producing hyperalgesia and hyperkatifeia, which drive pronounced drug-seeking behavior via processes of negative reinforcement. Hyperkatifeia (derived from the Greek "katifeia" for dejection or negative emotional state) is defined as an increase in intensity of the constellation of negative emotional or motivational signs and symptoms of withdrawal from drugs of abuse. In animal models, repeated extended access to drugs or opioids results in negative emotion-like states, reflected by the elevation of reward thresholds, lower pain thresholds, anxiety-like behavior, and dysphoric-like responses. Such negative emotional states that drive negative reinforcement are hypothesized to derive from the within-system dysregulation of key neurochemical circuits that mediate incentive-salience and/or reward systems (dopamine, opioid peptides) in the ventral striatum and from the between-system recruitment of brain stress systems (corticotropin-releasing factor, dynorphin, norepinephrine, hypocretin, vasopressin, glucocorticoids, and neuroimmune factors) in the extended amygdala. Hyperkatifeia can extend into protracted abstinence and interact with learning processes in the form of conditioned withdrawal to facilitate relapse to compulsive-like drug seeking. Compelling evidence indicates that plasticity in the brain pain emotional systems is triggered by acute excessive drug intake and becomes sensitized during the development of compulsive drug taking with repeated withdrawal. It then persists into protracted abstinence and contributes to the development and persistence of compulsive opioid-seeking behavior.

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阿片类药物成瘾的神经生物学：对手过程、过度兴奋和负强化

阿片类药物是强大的药物，可以篡夺和压制内源性阿片类药物的奖赏功能，并通过同一奖赏系统内的分子和神经回路神经适应产生显着的耐受性和戒断性。然而，它们也会使大脑系统产生压力和疼痛（躯体和情绪），同时产生痛觉过敏和过度紧张，通过负强化过程驱动明显的寻求药物行为。Hyperkatifeia（源自希腊语“katifeia”，表示沮丧或消极情绪状态）被定义为消极情绪或动机迹象和滥用药物戒断症状的强度增加。在动物模型中，重复使用药物或阿片类药物会导致类似负面情绪的状态，表现为奖励阈值的升高，降低疼痛阈值、焦虑样行为和烦躁样反应。这种驱动负强化的负面情绪状态被假设是源于关键神经化学回路的系统内失调，这些回路介导腹侧纹状体中的激励显着和/或奖励系统（多巴胺、阿片肽）以及系统间扩展杏仁核中的脑应激系统（促肾上腺皮质激素释放因子、强啡肽、去甲肾上腺素、下丘脑分泌素、加压素、糖皮质激素和神经免疫因子）。Hyperkatifeia 可以扩展到长期禁欲，并以有条件戒断的形式与学习过程相互作用，以促进复发到强迫性药物寻求。令人信服的证据表明，脑痛情绪系统的可塑性是由急性过量服用药物引发的，并在反复戒断的强迫性药物服用过程中变得敏感。然后它会持续到长期的禁欲状态，并有助于强迫性阿片类药物寻求行为的发展和持续。