HCN channel inhibitor induces ketamine-like rapid and sustained antidepressant effects in chronic social defeat stress model
Neurobiology of Stress August 1, 2023 Min Cai, Yingbo Zhu, M. R. Shanley et al.
A single dose of the HCN channel inhibitor DK-AH 269 (cilobradine) produces rapid and sustained antidepressant-like effects in mice subjected to chronic social defeat stress, lasting up to 13 days. The compound reduces pathological HCN-mediated currents and abnormal hyperactivity of dopamine neurons in the ventral tegmental area. Treated mice showed normalized social behavior, restored sucrose preference, and less immobility in the forced swim test compared to vehicle-treated animals. These effects parallel those of a single dose of ketamine, suggesting HCN channels as a novel target for fast-acting, long-lasting antidepressants.