Framework for internal sensation of pleasure using constraints from disparate findings in nucleus accumbens.

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.