Role of CaMKII/CREB pathway in rapid-antidepressant-like effect: comparison of ketamine with rapastinel.
Experimental brain research May 4, 2025 Ceyda Özler, Esra Özkan, Narges Shomalizadeh et al. 1 citation
Ketamine and rapastinel both produce rapid and sustained antidepressant-like effects in mice, despite having opposing actions on the NMDAR. Using a chronic unpredictable mild stress model in 46 male mice, the study found that both drugs restored reduced BDNF concentrations in the prefrontal cortex and hippocampus and reduced anhedonia and passive coping behavior. A CaMKII inhibitor, TatCN21, unexpectedly enhanced rapastinel's effects but blocked ketamine's effects, indicating that the CaMKII/CREB pathway plays a differential role in mediating these antidepressant-like actions. The findings suggest distinct mechanisms for these two rapid-acting antidepressants.