Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatr. Oct 19, 2021; 11(10): 681-695
Published online Oct 19, 2021. doi: 10.5498/wjp.v11.i10.681
Framework for internal sensation of pleasure using constraints from disparate findings in nucleus accumbens
Kunjumon Ittira Vadakkan
Kunjumon Ittira Vadakkan, Division of Neuroscience, Neurosearch Center, Toronto M5S2M3, Ontario, Canada
Author contributions: Vadakkan KI conceived the idea, drew the figures and wrote the manuscript.
Conflict-of-interest statement: United States patent number 9477924 pertains to an electronic circuit model of the inter-postsynaptic functional LINK.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Kunjumon Ittira Vadakkan, MBBS, MD, MSc, PhD, Senior Scientist, Division of Neuroscience, Neurosearch Center, 167 Brunswick Street, Toronto M5S2M3, Ontario, Canada.
Received: May 3, 2021
Peer-review started: May 3, 2021
First decision: June 17, 2021
Revised: June 27, 2021
Accepted: September 2, 2021
Article in press: September 2, 2021
Published online: October 19, 2021

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.

Keywords: Pleasure, Internal sensation, Mind, Memory, Long-term potentiation, Long-term depression, Nucleus accumbens, Drug addiction

Core Tip: Pleasure has been studied by examining animal behaviour and its correlations with molecular and electrophysiological changes. Drugs of abuse generate pleasure along with several seemingly unrelated changes in nucleus accumbens (NAc). When pleasure was examined as a first-person inner sensation, it was possible to arrive at a framework of a causal mechanism for its generation that can also provide inter-connected mechanistic explanations for long-term depression (LTD) in NAc in naïve animals, impaired ability to induce LTD in addicted state, attenuation of postsynaptic potentials by both cocaine and dopamine, and reduced firing of medium spiny neurons in NAc by dopamine. Findings made by this work are testable.