Genetic ablation of the isoform γ of PI3K decreases antidepressant efficacy of ketamine in male mice.
IBRO neuroscience reports December 1, 2024 Gabriela N Vaz, Flávia C Turcato, Isabel A V Lima et al.
Mice lacking the PI3Kγ gene did not respond to standard doses of ketamine or to classic antidepressants such as imipramine and fluoxetine, as measured by the forced swimming test. This unresponsiveness required a chronic deficiency of the PI3Kγ-mediated pathway, not just acute inhibition. The findings suggest PI3Kγ plays a role in antidepressant activity and may be involved in treatment resistance observed in some patients with major depressive disorder.