|
1000
|
Abstract/Summary
|
-
The project centers on the neurobiological mechanisms underlying motivational deficits in depression, focusing on dopamine 2 receptor (D2R) function in the ventral striatum and its interaction with glucose metabolism.Motivational deficits are a hallmark of major depression, characterized by diminished interest in activities, reduced energy, and an imbalance in effort-reward motivation. The mesolimbic dopamine system, plays a critical role in these processes. Evidence from human imaging studies and animal models suggests that disruptions in D2R signaling are linked to motivational impairments. For instance, stress models like chronic social defeat (CSD) in mice demonstrate that D2R dysfunction in the ventral striatum can lead to reward-seeking impairments and other depression-like symptoms. Additionally, disturbances in glucose metabolism appear to interact with D2R dysfunction, exacerbating motivational deficits. Research indicates that chronic stress induces hyperglycemia both peripherally and centrally, including the ventral striatum, which may disrupt the effort-reward balance.In conclusion, striatal D2R signaling may be important for effort-based motivation by directly influencing the mesolimbic dopamine system and glucose metabolism. The project aims to elucidate these interactions using animal models to advance understanding and treatment of depression-related motivational impairments.
|
