Depression in humans often stems from milder stressors over longer periods of time. Tye and Deisseroth used optogenetics to probe reward circuit workings related to depression-like behaviors in rodents exposed to stressors like white noise, crowded housing, or continuous darkness or illumination. Exposure to some of these milder stressors lasted 10 weeks, compared to the 10-days of social defeat stress.
"We sought to mimic gradual, stress-induced transitions to depressed-like states, as are often seen clinically," explained Deisseroth, who is a practicing psychiatrist as well as a neuroscientist.
In contrast to the Han-Nestler results after social defeat stress, following 10 weeks of unpredictable chronic mild stress, optogentically inducing high firing rates in VTA dopamine neurons instantly reversed such depression-like behaviors induced by chronic mild stressors and vice versa. Also opposite to the social defeat stress findings, optogenetically inhibiting VTA dopamine neurons induced depression-like states.
"The variable effects that stressors of different types induce in the dopamine system may point to the need for distinct treatment strategies for patients whose depressions stem from different types of experiences," said Tye, who is leading a research group studying the neural underpinnings of motivational and emotional processing.
When Tye and Deisseroth infused agents that block binding of the chemical messenger glutatmate in the nucleus accumbens, they produced an antidepressant response mice struggled more to escape the stressor. They note that this is consistent with the effects of the fast-acting antidepressant ketamine, which similarly blocks glutamate.
While optogenetics is providing insights into rapid antidepressant mechanisms, the technique is not suitable for t
|Contact: Jules Asher|
NIH/National Institute of Mental Health