Clinical studies have demonstrated that ketamine and agmatine initially function by selectively blocking a subset of NMDA receptors on GABAergic interneurons, which leads to disinhibition of glutamatergic target neurons, a surge in extracellular glutamate accompanied by elevated glutamatergic synaptic transmission (78, 79).Our previous results suggest that the utilization of VO-OHpic, known as a PTEN inhibitor, may offer therapeutic advantages in the treatment of depression-like behaviors and PFC neuron atrophy. This evidence concerns the gene PTEN and major depressive disorder.