Recent Advances in Drug Addiction Research and Clinical Applications. Chapter 1: Circuits Regulating Pleasure and Happiness: A Focus on Addiction, Beyond the Ventral Striatum

Abstract

A recently developed anatomical model describes how the intensity of reward-seeking and misery-fleeing behaviours is regulated. The first type of behaviours is regulated within an extrapyramidal cortical–subcortical circuit containing as first relay stations, the caudate nucleus, putamen and core of the accumbens nucleus. The second type of behaviours is controlled by a limbic cortical–subcortical circuit with as first stations, the centromedial amygdala, extended amygdala, bed nucleus of the stria terminalis and shell of the accumbens nucleus. We hypothesize that sudden cessation of hyperactivity of the first circuit results in feelings of pleasure and of the second circuit in feelings of happiness. The insular cortex has probably an essential role in the perception of these and other emotions. Motivation to show these behaviours is regulated by monoaminergic neurons projecting to the accumbens from the midbrain: dopaminergic ventral tegmental nuclei, adrenergic locus coeruleus and serotonergic upper raphe nuclei. The activity of these monoaminergic nuclei is in turn regulated through a ventral pathway by the prefrontal cortex and through a dorsal pathway by the medial and lateral habenula. The habenula has this role since the first vertebrate human ancestors with a brain comparable to that of modern lampreys. The lateral habenula promotes or inhibits reward-seeking behaviours depending upon the gained reward being larger or smaller than expected. It is suggested that the ventral pathway is essential for maintaining addiction based on the observation of specific cues, while the dorsal pathway is essential for becoming addicted and relapsing during periods of abstinence.