Stress and dopamine dysfunction in the brain: a role for glucose-mediated motivational deficits.

• Applicant: Michael van der Kooij, Ph.D.
• Subject Area: Biological Psychiatry
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 457638664

Motivational deficits are central to many stress-related mental disorders, but the underlying neurobiological mechanisms are incompletely understood. Multiple lines of evidence point to the involvement of the mesolimbic system in motivational processes. In particular, intact dopamine 2 receptor (D2R) function in the nucleus accumbens (NAc) emerges as a critical component in the maintenance of a healthy effort-reward balance; perturbations at this level may underlie motivational impairments, as found in depression. Other evidence suggests that in the NAc, disturbances in glucose metabolism, which is also seen with depression, may be linked to alterations in D2R signaling. Chronic social defeat (CSD) stress in mice models several aspects of depression including motivational deficits. Using this CSD mouse model we will test the importance of the D2R, glucose metabolism and their interactions in the NAc for effort-based reward motivation

• DFG Programme: Research Grants