<p>Ascorbate, a potent reducing agent highly concentrated in the brain, prevents neuronal oxidative damage and functions as a neuromodulator. Disrupted ascorbate homeostasis has been linked to neurological disorders, including Alzheimer’s disease. However, the in vivo mechanisms regulating brain ascorbate levels remain largely unexplored. Here, we demonstrate that serotonin and photic signaling jointly modulate extracellular ascorbate levels in the rat brain. Using in vivo microdialysis, we observed circadian rhythms in both serotonin metabolites and ascorbate levels in the thalamus of freely moving rats. Ascorbate exhibited marked photosensitivity, decreasing under light exposure and recovering in darkness. Serotonin depletion disrupted these circadian rhythms and abolished ascorbate’s photosensitivity. These findings suggest that brain ascorbate dynamics are regulated by both serotonergic activity and environmental light, highlighting a novel interplay between neural signaling and redox systems in the thalamus.</p>