The University of Osaka · Neuroscience
Professor Yukio Ago's research lab focuses on the neurochemical and neuropharmacological mechanisms underlying psychiatric disorders and neurodegenerative diseases. The lab investigates the roles of monoaminergic systems—particularly serotonin, dopamine, and acetylcholine—in behavior, cognition, and psychiatric pathophysiology. Key research directions include the modulation of neurotransmitter systems by drugs such as galantamine and ketamine, the neurochemical basis of behavioral sensitization, and the impact of early-life stress (e.g., isolation rearing) on brain function and mental health. The lab integrates preclinical models with neurochemical and behavioral analyses to explore novel therapeutic targets for schizophrenia, depression, addiction, and Alzheimer’s disease.
Figures are computed from collected data and may differ slightly.
Several lines of evidence suggest that cholinergic deficits may contribute to the pathophysiology of psychiatric disorders as well as Alzheimer's disease. There is growing clinical evidence that galantamine, currently used for the treatment of Alzheimer's disease, may improve cognitive dysfunction and psychiatric illness in schizophrenia, major depression, bipolar disorder, and alcohol abuse. Since galantamine is a rather weak acetylcholinesterase inhibitor, but has additional allosteric potenti
(R)-Ketamine strongly activates the prefrontal serotonergic system through an AMPA receptor-independent mechanism. (S)-Ketamine-induced serotonin and dopamine release was AMPA receptor-dependent. These findings provide a neurochemical basis for the underlying pharmacological differences between ketamine enantiomers and their metabolites.
Repeated administration of psychostimulants elicits a progressive enhancement of locomotor activity known as behavioral sensitization. Central dopamine (DA) neurons play key roles as the neural substrates mediating behavioral sensitization, but the role of the serotonin (5-HT) system in the sensitization is not fully elucidated. We have recently demonstrated that osemozotan, a specific 5-HT(1A)-receptor agonist, and ritanserin, a 5-HT(2)-receptor antagonist, inhibited the expression and developm
Serotonin (5-HT)1A receptors modulate in vivo release of brain monoaminergic neurotransmitters which may be involved in isolation-induced aggressive behavior. The present study examined the effect of isolation rearing on the 5-HT1A receptor-mediated modulation of dopamine (DA), 5-HT and noradrenaline (NA) release in the frontal cortex of mice. The selective 5-HT1A receptor agonist (S)-5-[-[(1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3-benzodioxole HCl (MKC-242) increased the release of DA and N
The behavior of isolation-reared mice has not yet been studied in the staircase test. The present study examined the effects of anxiolytic or anxiogenic agents and isolation rearing on the behavior of ddY (outbred) strain mice in the staircase test. Diazepam and phenobarbital increased the number of steps climbed, but did not affect rearing behavior in group-reared mice. FG-7142, a benzodiazepine inverse agonist, significantly increased the number of rearing with no changes in the number of step
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