National Institute of Mental Health 5R01MH063266-25

Roles of nucleus accumbens CREB and Kappa function in depression

The award supports research on how stress affects CREB and KOR systems in brain motivation circuits related to depression, aiming to inform new treatments and understand stress resilience, especially in the context of immune activation during early brain development.

Description

This program examines how stress changes the function of CREB and kappa-opioid receptor (KOR) systems in brain motivation circuits, and how these changes affect behavior. This line of work has provided a foundation for clinical trials of KOR antagonists to treat depression, an innovative approach which thus far shows great promise. Major goals include exploring whether alterations in CREB and KOR signaling are involved in the long-lasting pro-depressive effects caused by immune system activation during early brain development, a form of stress occurring widely during the COVID-19 pandemic, while examining factors that control stress susceptibility and resilience in animal models that are chosen because they use measurements and endpoints that are the same as used in humans.

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