Dopamine D2 Receptors and Its Downstream Signaling in Compulsive Eating.

Abstract

Obesity has become a major public health crisis and serves as an underlying condition for other chronic metabolic diseases. The dysregulation of the inhibitory and regulatory mechanisms of the mesolimbic dopamine system, particularly dopamine D2 receptors (D2Rs), plays a critical role in driving excessive food consumption and compulsive eating habits. Based on the current literature, chronic consumption of high-fat foods elicits hedonic sensations and has the potential to downregulate and desensitize D2Rs, impairing their signaling and inhibitory action. This impairment thereby alters the downstream signaling of the D2Rs, involving the inhibition of adenylyl cyclase and the associated cascade. Although individual components of this proposed pathway have been studied, a comprehensive synthesis has not been established. This review aims to explore the relationship between D2R downregulation and desensitization and their effects on the downstream signaling cascade. We hypothesize that alterations in this pathway may lead to the dysregulation of the expression of orexigenic and anorexigenic neuropeptides, contributing to binge-eating behaviors.