Topic: antidepressant effects

Several drugs of abuse have recently been shown clinically to have long-lasting antidepressant effects. Psilocybin and ketamine induce antidepressant effects which last for days or weeks after a single dose, yet their pharmacology is distinct. Psilocybin is a classical psychedelic which acts via 5-HT2A receptor agonism, and ketamine is a NMDA receptor antagonist with dissociative hallucinatory properties. Our goal was to increase our understanding of acute drug effects in mice. We treated wildtype mice with psilocybin (1 mg/kg, i.p.) or ketamine (30 mg/kg, i.p.) and analyzed their behavior in

Ketamine, an open-channel blocker of the N-methyl-D-aspartate receptor (NMDAR), has been shown to have rapid and sustained antidepressant effects after a single sub-anesthetic dose. Among its two enantiomers, (S)-ketamine acts more potently at NMDARs than (R)-ketamine, and its use as an antidepressant was approved by the FDA in 2019. Given that the mechanism underlying ketamine’s sustained antidepressant action remains unclear, we investigated if (S)-ketamine has any long-term effect on NMDAR-mediated synaptic transmission. In extracellular recordings from the CA1 region of mouse hippocampal s

The prefrontal cortex is one of the most commonly studied structures in depression. Synaptic loss and prefrontal circuits deficits have been widely described in depression physiopathology, and their restoration by antidepressant drugs is at the center of their therapeutic effect. Aims: This project aims to test the antidepressant potential of a specific manipulation of prefrontal circuits. Methods: Using the Chronic Despair Model (CDM) of depression, and the DREADDs chemogenetic technique, we counteracted the hypofrontality characteristic of a depressive-like state, and assessed the behavioura