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Resilience factor low in depression, protects mice from stress
Date:5/16/2010

quickly followed up and translated into potential clinical applications."

DeltaFosB is more active in the reward hub, called the nucleus accumbens (see diagram below), than in any other part of the brain. Chronic use of drugs of abuse or even natural rewards like excess food, sex or exercise can gradually induce increasing levels of this transcription factor in the reward hub. Nestler and colleagues have shown that this increase in deltaFosB can eventually lead to lasting changes in cells that increase rewarding responses to such stimuli, hijacking an individual's reward circuitry addiction.

The new study in mice and human post-mortem brains confirms that the same reward circuitry is similarly corrupted (though to a lesser degree than with drugs of abuse) in depression via effects of stress on deltaFosB.

Depressed patients often lack motivation and the ability to experience reward or pleasure and depression and addiction often go together. Indeed, mice susceptible to the depression-like syndrome show enhanced responses to drugs of abuse, the researchers have found.

But the similarity ends there. For, while an uptick in deltaFosB promotes addiction, the researchers have determined that it also protects against depression-inducing stress. It turns out that stress triggers the transcription factor in a different mix of nucleus accumbens cell types working through different receptor types than do drugs and natural rewards, likely accounting for the opposite effects.

The researchers explored the workings of deltaFosB in a mouse model of depression. Much as depressed patients characteristically withdraw from social contact, mice exposed to aggression by a different dominant mouse daily for 10 days often become socially defeated; they vigorously avoid other mice, even weeks later.

Among key findings in the brain's reward hub:

  • The amount of deltaFosB induced by the stress determined suscept
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Contact: Jules Asher
NIMHpress@nih.gov
301-443-4536
NIH/National Institute of Mental Health
Source:Eurekalert  

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