VTA Dopamine Neurons and Depressive Behaviors

The findings of Tye et al. (2012) and Chaundhury et al. (2012) reflect the extraordinary complexity of the VTA domamine system as relates to the effects of stress on depression. Chaundhury et al. explored the role of optogenetic stimulation in regulating resilience or susceptibility to social stress, as well as the projection pathways involved. Using social-defeat/social interaction and sucrose preference models to represent depressive phenotypes of social avoidance and anhedonia, they argue that optogenetic stimulation of phasic VTA dopamine neuronal firing rapidly produced a susceptible phenotype while tonic firing and the control did not. Similarly, phasic activation of VTA neurons to the nucleus accumbens (NAc) provoked susceptibility to stress, while activation of the medial prefrontal cortex (mPFC) did not. Furthermore, inhibition of the VTA-NAc produced the resilient phenotype, while inhibition of the VTA-mPFC induced susceptibility.

Contrastingly, Tye et al. (2012) used chronic mild stress (CMS) and sucrose preference as models for motivation and anhedonia as related to a depressive phenotype. They found that optogenetic phasic stimulation increased escape related behavior and reversed the anhedonia produced by CMS, while inhibition of VTA dopamine induces depression.

As indicated by the results, these two studies have yielded quite opposite conclusions regarding optogenetic VTA dopamine neuronal stimulation and inhibition in regards to producing or reversing depressive phenotypes. For this reason, it is crucial to acknowledge the role of the stress models in terms of varying exposure context and level of stress, as both authors acknowledge. For example, the social defeat model lasted 10 days, while the CMS lasted 12 weeks. Importantly, both authors agree upon the pathway involved, and the reversibility and rapid effect of optogenetic VTA dopamine alterations on depressive phenotypes. Interestingly, Chaundhury et al. (2012) mentioned the need for future research on the influence of non-dopamine neurons on the stress response in these models. Tye et al. (2012) tapped into this area by exploring the effect of glutamate in the NAc in comparison to dopamine in mediating the stress response to TST. While dopamine seems to be the most influential neurotransmitter in these studies, future research could focus on isolating the neuronal types involved in the depression phenotype induced from stress models.