Targeting D₂ receptor signaling pathways in mice as a chance to improve cognitive plasticity in neuropsychiatric disorders

The idea

As life expectancy rises, cases of cognitive deficits-ranging from mild impairments to severe dementias-are becoming increasingly common. Such deficits also occur in psychiatric disorders like depression and schizophrenia, where they worsen symptoms and impede treatment. Sigma-1 receptors, specialized proteins involved in neuronal communication and resilience, have emerged as promising targets for new therapies. While these receptors are known to support memory, their role in higher cognitive processes such as cognitive flexibility remains less understood.

Our approach

This project investigates whether activating sigma-1 receptors can restore cognitive flexibility disrupted by glutamatergic system dysfunction, a mechanism implicated in multiple brain disorders. Using advanced, translational touchscreen-based behavioral testing combined with molecular analyses, the study examines how sigma-1 receptor modulation influences executive functions in male mice.

Why it matters

The findings aim to uncover new therapeutic strategies for enhancing complex cognitive functions, with potential benefits for individuals affected by neuropsychiatric and neurodegenerative conditions.

Grant number: N42/DBS/000409