Pharmacological Perspective on the Neurobiology of PI3K-Akt-mTOR Signalling in Opioid Dependence.

Aditi Singh, Heena Khan, Amarjot Kaur Grewal, Kamal Dua, Sachin Kumar Singh, Thakur Gurjeet Singh
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Abstract

Opioid addiction is a condition of the central nervous system that occurs as a result of using opiate-based substances, which can be either natural or synthetic chemicals. These have effects identical to those of morphine and work by interacting with opioid receptors such as morphine, heroin, opium, buprenorphine, and Oxycontin. Dopamine has been suggested to play a role in the mechanisms linked to opioid addiction. Additionally, neurotransmitters such as serotonin, norepinephrine, glutamate, and GABA may also have a significant impact. These processes play a critical role in the formation of brain circuits that are involved in the development of addictive behavior. The PI3K-Akt-mTOR pathway is widely recognized as an essential regulator of the effects induced by neurotransmitters on synaptic plasticity, protein synthesis, and cellular responses. This interplay has considerable importance in the development and persistence of opioid addiction, impacting several domains, including reward processing, stress reactivity, and brain plasticity. The understanding of these neurochemical modifications provides vital insights into the underlying mechanisms of addiction and presents potential pathways for treatments. The review enlisted the clinical trials of different types of opioid addiction or dependence. The review offers a succinct summary of many studies that establish a correlation between the PI3K/Akt-mTOR signaling pathway and various receptors implicated in multiple forms of opioid-related dependency.

阿片类药物依赖中PI3K-Akt-mTOR信号通路神经生物学的药理研究
阿片类药物成瘾是一种中枢神经系统的状况,是使用阿片类物质的结果,这些物质可以是天然的,也可以是合成的化学物质。这些药物的作用与吗啡相同,通过与吗啡、海洛因、鸦片、丁丙诺啡和奥施康定等阿片受体相互作用而起作用。多巴胺被认为在与阿片类药物成瘾相关的机制中发挥作用。此外,神经递质如血清素、去甲肾上腺素、谷氨酸和GABA也可能有显著影响。这些过程在大脑回路的形成中起着至关重要的作用,而大脑回路与成瘾行为的发展有关。PI3K-Akt-mTOR通路被广泛认为是神经递质诱导突触可塑性、蛋白质合成和细胞反应的重要调节因子。这种相互作用在阿片类药物成瘾的发展和持续中具有相当重要的意义,影响几个领域,包括奖励处理、应激反应和大脑可塑性。对这些神经化学修饰的理解为成瘾的潜在机制提供了重要的见解,并为治疗提供了潜在的途径。该综述纳入了不同类型阿片类药物成瘾或依赖的临床试验。该综述简要总结了许多研究,这些研究建立了PI3K/Akt-mTOR信号通路与多种形式的阿片类药物相关依赖所涉及的各种受体之间的相关性。
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