The antidepressant-like activity of ketamine in the rat chronic mild stress model requires activation of cortical 5-HT 1A receptors.
Behavioural pharmacology June 1, 2025 Ronan Depoortère, Mariusz Papp, Piotr Gruca et al. 2 citations
Ketamine rapidly reverses depression-like symptoms in rats exposed to chronic mild stress, including loss of pleasure and working memory deficits, when given systemically or directly into the prefrontal cortex. Blocking serotonin 5-HT1A receptors in the prefrontal cortex with WAY-100635 prevents these effects, showing that ketamine's rapid antidepressant and pro-cognitive actions require activation of these receptors. The findings suggest that drugs directly targeting prefrontal cortex 5-HT1A receptors could provide rapid antidepressant effects and improve cognitive deficits without ketamine's side effects or need for clinical supervision.