Vadakkan Kunjumon Ittira
Division of Neuroscience, Neurosearch Center, Toronto M5S2M3, Ontario, Canada.
World J Psychiatry. 2021 Oct 19;11(10):681-695. doi: 10.5498/wjp.v11.i10.681.
It is necessary to find a mechanism that generates first-person inner sensation of pleasure to understand what causes addiction and associated behaviour by drugs of abuse. The actual mechanism is expected to explain several disparate findings in nucleus accumbens (NAc), a brain region associated with pleasure, in an interconnected manner. Previously, it was possible to derive a mechanism for natural learning and explain: (1) Generation of inner sensation of memory using changes generated by learning; and (2) Long-term potentiation as an experimental delayed scaled-up change by the same mechanism that occur during natural learning. By extending these findings and by using disparate third person observations in NAc from several studies, present work provides a framework of a mechanism that generates internal sensation of pleasure that can provide interconnected explanations for: (1) Ability to induce robust long-term depression (LTD) in NAc from naïve animals; (2) Impaired ability to induce LTD in "addicted" state; (3) Attenuation of postsynaptic potentials by cocaine; and (4) Reduced firing of medium spiny neurons in response to cocaine or dopamine. Findings made by this work are testable.
有必要找到一种能产生第一人称内在愉悦感的机制，以了解滥用药物导致成瘾及相关行为的原因。预期实际机制能够以相互关联的方式解释伏隔核（NAc）中几个不同的发现，伏隔核是一个与愉悦感相关的脑区。此前，有可能推导出一种自然学习机制并解释：（1）利用学习产生的变化来产生记忆的内在感觉；（2）长时程增强作为一种实验性延迟放大变化，其机制与自然学习过程中发生的机制相同。通过扩展这些发现，并利用来自多项研究的伏隔核中不同的第三人称观察结果，本研究提供了一种产生愉悦内在感觉的机制框架，该框架能够对以下方面提供相互关联的解释：（1）从幼稚动物诱导伏隔核中强大的长时程抑制（LTD）的能力；（2）“成瘾”状态下诱导LTD的能力受损；（3）可卡因对突触后电位的减弱作用；（4）中棘神经元对可卡因或多巴胺反应的放电减少。本研究的发现是可检验的。
