Emerging Role for Nucleus Accumbens Medium Spiny Neuron Subtypes in Depression

Biol Psychiatry. 2017 Apr 15;81(8):645-653. doi: 10.1016/j.biopsych.2016.09.007. Epub 2016 Sep 15.


The ventral striatum (nucleus accumbens) and its role in mood, reward, and motivation has been the focus of significant research. Despite this interest, little work has addressed cell type-specific distinctions in medium spiny neurons (MSNs), the main projection neurons in the nucleus accumbens and dorsal striatum, and their function in relation to stress and depression. Previous work has shown opposing roles for D1 and D2 receptor MSN subtypes in depression-like outcomes to stress, particularly in regard to repeated neuronal stimulation and excitatory transmission. Yet the mechanisms of action are still unknown. We discuss potential mechanisms by which MSN subtype function promotes dichotomous behavioral outcomes caused by differences in cellular plasticity, subcellular signaling pathways, and genetic expression. This review aims to address our current understanding about the role of nucleus accumbens MSN subtypes in stress-related depression behavior and speculates on how currently understood mechanisms contribute to factors that control the activity of MSNs.

Keywords: Deep brain stimulation; Excitatory synaptic transmission; Medium spiny neuron; Social defeat; Stress; Striatum.

Publication types

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

MeSH terms

  • Animals
  • Brain / physiopathology
  • Depression / physiopathology
  • Depressive Disorder / complications
  • Depressive Disorder / physiopathology*
  • Excitatory Postsynaptic Potentials
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neural Pathways / physiopathology
  • Neurons / physiology*
  • Nucleus Accumbens / physiopathology*
  • Receptors, Dopamine D1 / physiology
  • Receptors, Dopamine D2 / physiology
  • Social Behavior
  • Stress, Psychological / complications
  • Stress, Psychological / physiopathology*


  • Receptors, Dopamine D1
  • Receptors, Dopamine D2