Publications by authors named "Shinji Tsukada"
Alternatives to ketamine without psychotomimetic properties for the treatment of depression have attracted much attention. Here, we examined the anti-despair and anti-anhedonia effects of the ketamine metabolites (S)-norketamine ((S)-NK), (R)-NK, (2S,6S)-hydroxynorketamine, and (2R,6R)-hydroxynorketamine in a mouse model of depression induced by social isolation. All ketamine metabolites examined had acute (30 min after administration) anti-despair-like effects in the forced swim test, but only (S)-NK showed a long-lasting (1 week) effect.
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- Clinical studies indicate that ketamine is effective as a rapid and long-lasting antidepressant, leading researchers to explore its metabolites for similar effects.
- This study specifically compared the effects of four ketamine metabolites on a mouse model of depression induced by chronic corticosterone treatment.
- Results showed that only the metabolites (S)-norketamine and (2S,6S)-hydroxynorketamine exhibited significant antidepressant-like effects, while others did not demonstrate any benefits.
Article Synopsis
- - The study explored how (R)-ketamine and (S)-ketamine, along with their metabolites, affect neurotransmitter levels, particularly in the prefrontal cortex of mice, highlighting their differing impacts on serotonin and dopamine release.
- - Results showed that (R)-ketamine significantly increased serotonin release more than (S)-ketamine, while (S)-ketamine led to a larger increase in dopamine levels; both enantiomers increased noradrenaline equally.
- - The findings suggest that (R)-ketamine activates the serotonergic system through mechanisms that don't involve AMPA receptors, while (S)-ketamine impacts neurotransmission differently, indicating unique pathways for each enantiomer's antidepressant effects.
Growing evidence suggests pivotal roles for epigenetic mechanisms in both animal models of and individuals with autism spectrum disorders (ASD). Neuron-restrictive silencer factor (NRSF) binds to neuron-restrictive silencing elements in neuronal genes and recruits co-repressors, such as mSin3, to epigenetically inhibit neuronal gene expression. Because dysregulation of NRSF is related to ASD, here we examined the effects of mS-11, a chemically optimized mimetic of the mSin3-binding helix in NRSF, on the behavioral and morphological abnormalities found in a mouse model of valproic acid (VPA)-induced ASD.
View Article and Find Full Text PDFRationale: Rodents exposed prenatally to valproic acid (VPA) exhibit autism spectrum disorder (ASD)-like behavioral abnormalities. We recently found that prenatal VPA exposure causes hypofunction of the prefrontal dopaminergic system in mice. This suggests that the dopaminergic system may be a potential pharmacological target for treatment of behavioral abnormalities in ASD patients.
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