Serotonergic transmission plays differentiated roles in the rapid and sustained antidepressant-like effects of ketamine.
British journal of pharmacology December 1, 2024 Yong-Yu Yin, Jiao-Zhao Yan, Qian-Qian Wei et al. 13 citations
Ketamine produces rapid antidepressant-like effects in mice within 60 minutes and increases brain serotonin levels. The sustained effects at 24 hours require an intact serotonin system: depleting serotonin or knocking out the serotonin synthesis enzyme Tph2 eliminated the 24-hour but not the 60-minute effects. Blocking AMPA receptors with NBQX also prevented the rise in serotonin and abolished the sustained antidepressant-like effects. Serotonergic neurotransmission is necessary for ketamine's lasting antidepressant action, and this mechanism involves AMPA receptors.