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Review
. 2014 Apr;39(7):1179-88.
doi: 10.1111/ejn.12490.

Stress and VTA synapses: implications for addiction and depression

Abigail M Polter  1 , Julie A Kauer
Affiliations
Review

Stress and VTA synapses: implications for addiction and depression

Abigail M Polter et al. Eur J Neurosci. 2014 Apr.

Abstract

While stressful experiences are a part of everyone's life, they can also exact a major toll on health. Stressful life experiences are associated with increased substance abuse, and there exists significant co-morbidity between mental illness and substance use disorders [N.D. Volkow & T.K. Li (2004) Nat. Rev. Neurosci., 5, 963-970; G. Koob & M.J. Kreek (2007) Am. J. Psych., 164, 1149-1159; R. Sinha (2008) Annals N.Y. Acad. Sci., 1141, 105-130]. The risk for development of mood or anxiety disorders after stress is positively associated with the risk for substance use disorders [R. Sinha (2008) Annals N.Y. Acad. Sci., 1141, 105-130], suggesting that there are common substrates for vulnerability to addictive and affective disorders. Understanding the molecular and physiological substrates of stress may lead to improved therapeutic interventions for the treatment of substance use disorders and mental illnesses.

Keywords: depression; dopamine; reward; synaptic plasticity; ventral tegmental area.

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Conflict of interest statement

The authors declare that they do not have any conflict of interest.

Figures

Figure 1
Figure 1
Modulation of VTA synaptic plasticity by stress systems. A) At excitatory synapses, stress-induced activation of glucocorticoid receptors leads to an increase in the AMPA and NMDA ratio. B) CRF potentiates NMDA currents through activation of CRF2 receptors and downstream activation of PLC and PKC. C) Inhibitory synapses are potentiated via the retrograde messenger nitric oxide and activation of cGMP signaling. This plasticity is blocked by stress through activation of kappa opioid receptors. From (Saal et al., 2003; Ungless et al., 2003; Nugent et al., 2007; Daftary et al., 2009; Nugent et al., 2009; Niehaus et al., 2010; Graziane et al., 2013) GC: glucocorticoid, GR: glucocorticoid receptor, CRF: corticotrophin releasing factor, CRF-BP: CRF-binding protein, CRF2R: CRF receptor type 2, PLC: phospholipase C, PKC: protein kinase C,NOS: nitric oxide synathase, NO: nitric oxide, cGMP: cyclic guanosine monophosphate, κOR: kappa opioid receptor, dyn: dynorphin, PKG: protein kinase G
See this image and copyright information in PMC

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