Dual activity of HBK-15 – uncovering the cellular mechanisms underlying its rapid antidepressant and procognitive effects

The idea

Many antidepressants help improve mood, but few address the cognitive problems that often persist in depression. Difficulties with memory, focus, and learning can make recovery incomplete. We wanted to see whether one compound could do both - lift mood and support cognition - and to understand how this happens on a molecular level.

Our approach

We studied HBK-15, a methoxyphenylpiperazine derivative that showed fast antidepressant-like and memory-enhancing effects in rodents. Using behavioral tests that measure learning and different types of memory, we examined its impact on cognitive performance. In parallel, we analyzed key proteins involved in synaptic plasticity and memory formation to identify mechanisms that might explain these effects. We also explored how HBK-15 acts in female mice, since depression affects women more often and may involve sex-related differences in brain signaling.

Why it matters

Finding drugs that work faster and improve both mood and cognition could make antidepressant therapy more effective and lasting. Our study helps outline the biological pathways that might be targeted to achieve this dual effect.

Grant number: 2019/34/E/NZ7/00454