Pharmacology, Biochemistry and Behavior
December 9, 2019
Satoshi Deyama, R. Duman
181 citations
Depression is linked to reduced levels of neurotrophic factors like BDNF and VEGF, which contribute to neuronal atrophy in brain regions such as the prefrontal cortex and hippocampus, and to decreased adult neurogenesis. Conventional antidepressants partially reverse these deficits by inducing BDNF or VEGF but have limitations, including a delayed therapeutic response and low efficacy. Ketamine, an NMDA receptor antagonist, produces rapid (within hours) and sustained (up to a week) antidepressant effects in treatment-resistant depression and rodent models. In rodents, ketamine quickly increases BDNF and VEGF release in the medial prefrontal cortex and hippocampus, boosting spine synapses and hippocampal neurogenesis. These neurotrophic actions appear to underlie ketamine's rapid and sustained antidepressant effects, pointing toward development of faster-acting antidepressants with fewer side effects.
European Journal of Pharmacology
October 25, 2025
Satoshi Deyama, Kenji Mishiro, Munetaka Kunishima et al.
A single injection of (R)-ketamine at 30 mg/kg, but not 10 mg/kg, reduced marble burying—a measure of compulsive-like behavior—in male mice at 2 hours, 24 hours, and 7 days after treatment, without affecting general movement. (S)-ketamine at 10 mg/kg also reduced burying. Blocking L-type voltage-dependent calcium channels (L-VDCCs) with verapamil prevented the effect of (S)-ketamine but not of (R)-ketamine. Infusing verapamil directly into the ventromedial orbitofrontal cortex or ventromedial prefrontal cortex also blocked (S)-ketamine's effect. These findings suggest (R)-ketamine produces anticompulsive-like effects comparable to a 3-fold lower dose of (S)-ketamine, and that L-VDCC activation in those brain regions mediates the effects of (S)-ketamine but not (R)-ketamine.
Psychopharmacology
July 1, 2019
Shiho Ito, Satoshi Deyama, Masaki Domoto et al.
The synthetic cannabinoid 5F-AMB, when injected into the brain of mice, reduces anxiety and impairs the acquisition of recognition memory by activating CB1 receptors. Systemic injection severely reduces movement, an effect partially blocked by a CB1 antagonist. Infusion into the medial prefrontal cortex impairs memory acquisition but does not affect anxiety, suggesting other brain regions mediate the anxiolytic effect.
Psychopharmacology
August 1, 2018
Masaki Domoto, Hitoki Sasase, Shintaro Wada et al.
5F-AMB, a synthetic cannabinoid abused worldwide, reduces both excitatory and inhibitory signaling in layer V pyramidal neurons of the medial prefrontal cortex by activating CB1 receptors on presynaptic terminals. Bath application of 5F-AMB decreased the frequency of spontaneous and miniature excitatory and inhibitory postsynaptic currents, an effect blocked by the CB1 antagonist AM251. The suppression of excitatory transmission was greater than that of inhibitory transmission, shifting the balance toward net inhibition of these neurons. This inhibitory effect may contribute to the memory and consciousness impairments observed after inhalation of 5F-AMB.