Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain.
Instituto de Investigación Biomédica de Málaga (IBIMA), UGC Salud Mental, Hospital Regional Universitario de Málaga, Málaga, Spain.
Addict Biol. 2021 Mar;26(2):e12936. doi: 10.1111/adb.12936. Epub 2020 Jul 7.
Addiction is defined as the repeated exposure and compulsive seek of psychotropic drugs that, despite the harmful effects, generate relapse after the abstinence period. The psychophysiological processes associated with drug addiction (acquisition/expression, withdrawal, and relapse) imply important alterations in neurotransmission and changes in presynaptic and postsynaptic plasticity and cellular structure (neuroadaptations) in neurons of the reward circuits (dopaminergic neuronal activity) and other corticolimbic regions. These neuroadaptation mechanisms imply important changes in neuronal energy balance and protein synthesis machinery. Scientific literature links drug-induced stimulation of dopaminergic and glutamatergic pathways along with presence of neurotrophic factors with alterations in synaptic plasticity and membrane excitability driven by metabolic sensors. Here, we provide current knowledge of the role of molecular targets that constitute true metabolic/energy sensors such as AMPK, mTOR, ERK, or K in the development of the different phases of addiction standing out the main brain regions (ventral tegmental area, nucleus accumbens, hippocampus, and amygdala) constituting the hubs in the development of addiction. Because the available treatments show very limited effectiveness, evaluating the drug efficacy of AMPK and mTOR specific modulators opens up the possibility of testing novel pharmacotherapies for an individualized approach in drug abuse.
成瘾被定义为反复接触和强迫性寻求精神药物，尽管有不良影响，但在禁欲期后会导致复发。与药物成瘾相关的心理生理过程（获得/表达、戒断和复发）意味着在奖励回路（多巴胺能神经元活动）和其他皮质边缘区域的神经元中的神经递质传递发生重要改变，以及突触前和突触后可塑性和细胞结构（神经适应）发生变化。这些神经适应机制意味着神经元能量平衡和蛋白质合成机制发生重要变化。科学文献将药物诱导的多巴胺能和谷氨酸能途径的刺激以及神经营养因子的存在与代谢传感器驱动的突触可塑性和膜兴奋性的改变联系起来。在这里，我们提供了构成真正代谢/能量传感器的分子靶点（如 AMPK、mTOR、ERK 或 K）在成瘾不同阶段发展中的作用的最新知识，突出了构成成瘾发展中心的主要脑区（腹侧被盖区、伏隔核、海马体和杏仁核）。由于现有的治疗方法显示出非常有限的效果，评估 AMPK 和 mTOR 特异性调节剂的药物疗效为药物滥用的个体化治疗方法开辟了测试新的药物治疗的可能性。
