A potential role for microglia in stress- and drug-induced plasticity in the nucleus accumbens: A mechanism for stress-induced vulnerability to substance use disorder.

Stress is an important risk factor for the development of substance use disorder (SUD). Exposure to both stress and drugs abuse lead to changes in synaptic plasticity and stress-induced alterations in synaptic plasticity may contribute to later vulnerability to SUD. Recent developmental neuroscience studies have identified microglia as regulators of synaptic plasticity. As both stress and drugs of abuse lead to microglial activation, we propose this as a potential mechanism underlying their ability to change synaptic plasticity. This review focuses on three components of synaptic plasticity: spine density, brain-derived neurotrophic factor (BDNF) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor expression. Their roles in addiction, stress, and development will be reviewed, as well as possible mechanisms by which microglia could regulate their function. Potential links between stress, vulnerability to addiction, and microglial activity will be explored.