Stress-induced plasticity and functioning of ventral tegmental dopamine neurons

• Published in: Neuroscience and biobehavioral reviews Vol. 108; pp. 48 - 77
• Main Authors: Douma, Erik H., de Kloet, E. Ronald
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.01.2020
• Subjects: Adaptation; Adaptation, Psychological - physiology; Addiction; Animals; BDNF; Cognition; Coping; CRH; Depression; Dopamine; Dopaminergic Neurons - metabolism; Glucocorticoids; Habituation; Humans; Mesocorticolimbic system; Microglia; Nerve Net - metabolism; Nerve Net - physiopathology; Neurodegeneration; Neuronal Plasticity - physiology; Opioids; Prefrontal Cortex - metabolism; Prefrontal Cortex - physiopathology; Sex Characteristics; Stress; Stress, Psychological - metabolism; Stress, Psychological - physiopathology; Ventral tegmental area; Ventral Tegmental Area - metabolism; Ventral Tegmental Area - physiopathology; AMPA; Glucocorticoids; ACTH; mEPSC; PVN; Cognition; mGluR; NAc; PI3K; GSK3; Neurodegeneration; mTOR; ISDS; CUS; MR; DOR; NOPR; PKA; CMS; PKC; Microglia; MPAR; BNST; mPFC; BLA; PPTg; NE; CRH; GABA; NMDAR; VP; LTD; NO; VTA; IP3R; CRS; LTP; Habituation; Opioids; NMDA; Coping; Ventral tegmental area; GABAR; Adaptation; CSDS; Dopamine; BDNF; Mesocorticolimbic system; PLCγ; Depression; GR; IP3; Stress; HPA-axis; KOR; POMC; MOR; TH; Addiction; vHipp; PAG; N/OFQ; DA
• ISSN: 0149-7634; 1873-7528; 1873-7528
• DOI: 10.1016/j.neubiorev.2019.10.015

•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. 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.