The Regulation of Glutamate Transporter 1 in the Rapid Antidepressant-Like Effect of Ketamine in Mice
Frontiers in Behavioral Neuroscience March 2, 2022 Yaping Chen, Mengxin Shen, Xu Liu et al.
Blocking glutamate transporter 1 (GLT1) with dihydrokainic acid (DHK) prevents ketamine's antidepressant-like effects in mice and reduces phosphorylation of mTOR in the prefrontal cortex. Inhibiting AMPA receptors or L-type voltage-dependent calcium channels (L-VDCC) also abolishes ketamine's antidepressant-like effect. L-VDCC inhibition blocks ketamine-induced upregulation of GLT1 and BDNF, while AMPA receptor inhibition only reduces BDNF. GLT1 appears to be a critical presynaptic molecule in depression's pathophysiology and ketamine's mechanism, with AMPA receptors and L-VDCC both essential for the immediate antidepressant-like effect.