The Intertwined Roles of Circadian Rhythms and Neuronal Metabolism Fueling Drug Reward and Addiction.

Drug addiction is a highly prevalent and devastating disorder with few effective treatments, resulting in enormous burdens on family and society. The cellular and behavioral effects of drugs of abuse are related to their abilities to elevate synaptic dopamine levels. Midbrain dopaminergic neurons projecting from the ventral tegmental area to the nucleus accumbens play crucial roles in substance-induced neural and behavioral plasticity. Significantly, increasing work suggests that interplay between the brain circadian system and the cellular bioenergetic machinery in these dopamine neurons plays a critical role in mediating the actions of drugs of abuse. Here, we describe recent progress in elucidating the interconnections between circadian and metabolic systems at the molecular and cellular levels and their relationships to modulation of drug reward and addiction.