Stress-induced plasticity and functioning of ventral tegmental dopamine neurons

Highlights

• mPFC coordinates VTA-linked emotional-motivational valuation with stress-coping.

• CRH reduces, while opioids and glucocorticoids increase tonic VTA excitability.

• VTA-DA neurons degenerate during chronic stress after a transient rise in excitability.

• VTA-DA neurons are sexual dimorphic.

• VTA-DA dysfunction is a common substrate for obesity, depression, OCD, and addiction.

Abstract

The ventral tegmental area dopamine (VTA-DA) mesolimbic circuit processes emotional, motivational, and social reward associations together with their more demanding cognitive aspects that involve the mesocortical circuitry. Coping with stress increases VTA-DA excitability, but when the stressor becomes chronic the VTA-DA circuit is less active, which may lead to degeneration and local microglial activation. This switch between activation and inhibition of VTA-DA neurons is modulated by e.g. corticotropin-releasing hormone (CRH), opioids, brain-derived neurotrophic factor (BDNF), and the adrenal glucocorticoids. These actions are coordinated with energy-demanding stress-coping styles to promote behavioral adaptation. The VTA circuits show sexual dimorphism that is programmed by sex hormones during perinatal life in a manner that can be affected by glucocorticoid exposure. We conclude that insight in the role of stress in VTA-DA plasticity and connectivity, during reward processing and stress-coping, will be helpful to better understand the mechanism of resilience to breakdown of adaptation.