Fig. 2

Ketamine and RARα receptor agonists can regulate synaptic scaling through different pathways and exert antidepressant effects. A simplified overview of the antidepressant effects of ketamine and RARα receptor agonists through the regulation of synaptic scaling. Ketamine enhances the recruitment of postsynaptic GluA1/2, facilitating synaptic scaling and driving rapid antidepressant effects. Similarly, RARα receptor agonists directly activate retinoic acid receptors, which also leads to an increased recruitment of postsynaptic GluA1, thereby promoting synaptic scaling. This mechanism produces antidepressant effects comparable to those of ketamine. eEF2K elongation factor 2 kinase, eEF2 elongation factor 2, FMRP fragile X mental retardation protein, CaM calmodulin, CaN calcineurin, RALDH retinal dehydrogenase, BDNF brain-derived neurotrophic factor, GluA1/2 AMPA receptor subunits 1/2