Mesolimbic pathway in the context of "Olfactory tubercle"

The disease model of addiction describes an addiction as a disease with genetic, biological, neurological or environmental origin. The traditional medical model of disease requires only an abnormal condition causing distress, discomfort or dysfunction to an affected individual. The contemporary medical model partly attributes addiction to changes in the brain's mesolimbic pathway. The model also considers these diseases as a result of other biological, psychological or sociological entities, despite an incomplete understanding of their mechanisms. The common biomolecular mechanisms underlying addiction – CREB and ΔFosB – were reviewed by Eric J. Nestler in a 2013 review. Genetics and mental disorders may precipitate the severity of a drug addiction. It is estimated that 50% of healthy individuals developing an addiction can trace the cause to genetic factors.

Disorders of diminished motivation (DDM) are a group of disorders involving diminished motivation and associated emotions. Many different terms have been used to refer to diminished motivation. Often however, a spectrum is defined encompassing apathy, abulia, and akinetic mutism, with apathy the least severe and akinetic mutism the most extreme.

DDM can be caused by psychiatric disorders like depression and schizophrenia, brain injuries, strokes, and neurodegenerative diseases. Damage to the anterior cingulate cortex and to the striatum, which includes the nucleus accumbens and caudate nucleus and is part of the mesolimbic dopamine reward pathway, have been especially associated with DDM. Diminished motivation can also be induced by certain drugs, including antidopaminergic agents like antipsychotics, selective serotonin reuptake inhibitors (SSRIs), and cannabis, among others.

The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the nucleus accumbens septi, Latin for 'nucleus adjacent to the septum') is a region in the basal forebrain rostral to the preoptic area of the hypothalamus. The nucleus accumbens and the olfactory tubercle collectively form the ventral striatum. The ventral striatum and dorsal striatum collectively form the striatum, which is the main component of the basal ganglia. The dopaminergic neurons of the mesolimbic pathway project onto the GABAergic medium spiny neurons of the nucleus accumbens and olfactory tubercle. Each cerebral hemisphere has its own nucleus accumbens, which can be divided into two structures: the nucleus accumbens core and the nucleus accumbens shell. These substructures have different morphology and functions.

Different NAcc subregions (core vs shell) and neuron subpopulations within each region (D1-type vs D2-type medium spiny neurons) are responsible for different cognitive functions. As a whole, the nucleus accumbens has a significant role in the cognitive processing of motivation, aversion, reward (i.e., incentive salience, pleasure, and positive reinforcement), and reinforcement learning (e.g., Pavlovian-instrumental transfer); hence, it has a significant role in addiction. In addition, part of the nucleus accumbens core is centrally involved in the induction of slow-wave sleep. The nucleus accumbens plays a lesser role in processing fear (a form of aversion), impulsivity, and the placebo effect. It is involved in the encoding of new motor programs as well.