Potential roles for opioid receptors in motivation and major depressive disorder

Deficits in motivation are at the core of many neuropsychiatric disorders, including major depressive disorder (MDD). Research in MDD has been heavily focused on anhedonia and depression or negative/positive symptoms of depression, with less research attention focused on the dysregulation of motivational processes. Opioid receptors are widely distributed throughout the brain, particularly in areas implicated in motivation, especially the striatum, nucleus accumbens, medial prefrontal cortex, hippocampus, ventral tegmental area, hypothalamus, and amygdala. Mu, kappa, and delta opioid receptors (MOR, KOR, and DOR, respectively) and their endogenous ligands play an essential role in the regulation of mood, reward processing, and motivated behavior. This review will highlight the impact of opioids in motivational behavior with a particular focus on depression. An understanding of the neurobiology and neural circuits subserving motivational behavior will facilitate treatment of disorders that comprise reward deficits.