The molecular and cellular mechanisms of depression: a focus on reward circuitry

Mol Psychiatry. 2019 Dec;24(12):1798-1815. doi: 10.1038/s41380-019-0415-3. Epub 2019 Apr 9.


Depression is a complex disorder that takes an enormous toll on individual health. As affected individuals display a wide variation in their clinical symptoms, the precise neural mechanisms underlying the development of depression remain elusive. Although it is impossible to phenocopy every symptom of human depression in rodents, the preclinical field has had great success in modeling some of the core affective and neurovegetative depressive symptoms, including social withdrawal, anhedonia, and weight loss. Adaptations in select cell populations may underlie these individual depressive symptoms and new tools have expanded our ability to monitor and manipulate specific cell types. This review outlines some of the most recent preclinical discoveries on the molecular and neurophysiological mechanisms in reward circuitry that underlie the expression of behavioral constructs relevant to depressive symptoms.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Anhedonia / physiology
  • Animals
  • Depression / metabolism*
  • Depression / physiopathology*
  • Depressive Disorder, Major / metabolism
  • Depressive Disorder, Major / physiopathology
  • Disease Models, Animal
  • Humans
  • Motivation / physiology
  • Reward
  • Social Behavior
  • Weight Loss / physiology