A single dose combining a neuropeptide Y Y1 receptor agonist with ketamine enhanced memory consolidation and increased production of new neurons (neuroblasts) in the dorsal hippocampus of male rats, without affecting quiescent neural progenitors or astrocytes. The effects were linked to brain-derived neurotrophic factor and suggested the formation of NPY1R-TrkB heteroreceptor complexes, though this interaction requires further confirmation. The findings point to a potential therapeutic approach for neurodegenerative diseases.
A combination of an NPY1R agonist and Ketamine, given together to rodents, produced stronger antidepressant-like effects than either drug alone. The animals showed less immobility in a forced swimming test, a standard measure of antidepressant activity. This behavioral change was linked to increased formation of NPY1R/TrkB receptor complexes and higher levels of brain-derived neurotrophic factor (BDNF) in the ventral dentate gyrus of the hippocampus, along with increased neurogenesis. The results suggest that co-activating NPY1R and TrkB pathways may represent a novel therapeutic strategy for major depressive disorder that warrants further clinical investigation.