Yoshikatsu Masuda

Bio: Yoshikatsu Masuda is an academic researcher from Iwate Medical University. The author has contributed to research in topics: Acetylcholine & Monoamine neurotransmitter. The author has an hindex of 12, co-authored 42 publications receiving 436 citations.

Rapid determination of norepinephrine, dopamine, serotonin, their precursor amino acids, and related metabolites in discrete brain areas of mice within ten minutes by HPLC with electrochemical detection.

Abstract: A rapid and simple chromatographic procedure using HPLC with electrochemical detection is described for simultaneous determination of the substrates from precursor amino acids to metabolites related to synthesis and metabolism of three monoamine neurotransmitters--norepinephrine (NE), dopamine (DA), and 5-hydroxytryptamine (5-HT, serotonin)--in discrete brain areas of the mouse. Under the present instrumental and mobile phase conditions, the procedure permits simultaneous determination of three monoamines (NE, DA, and 5-HT), two precursor amino acids (tyrosine and tryptophan), and four respective metabolites (3-methoxy-4-hydroxyphenylglycol, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid) within 10 min in one chromatographic run. By varying column temperature, this procedure also permits simultaneous determination of 10-14 monoamine-related substrates including the nine substrates described above within 15-21 min. The validity of the present procedure is demonstrated by analyzing the effect of an alpha 2-adrenergic agonist (clonidine) and an alpha 2-antagonist (yohimbine) in mouse hypothalamus.

Rapid and simultaneous assay of monoamine neurotransmitters and their metabolites in discrete brain areas of mice by HPLC with Coulometric detection

Abstract: For simultaneous assay of the three monoamine neurotransmitters, norepinephrine, dopamine, and serotonin, and four respective metabolites in brain tissue, a rapid and simple method using high-performance liquid chromotography with coulometric detection is described. Because the present method permits the determination of these target substrates within 10 min or less in one chromotographic run, 150 samples can be analyzed using an autosampler and an integrator in a 24-h period. Within-run coefficients of variation for the target substrates in the standard solution and the whole brain sample were less than 3% and 2% (n = 40), respectively. The quantitative detection limits were 0.01-0.1 pmol. The present procedure was applied to measure the target substrates in several discrete brain areas in mice.

A rapid assay for neurotransmitter amino acids, aspartate, glutamate, glycine, taurine and γ-aminobutyric acid in the brain by high-performance liquid chromatography with electrochemical detection

Abstract: For simultaneous assay of the five neurotransmitter amino acids, Asp, Glu, Gly, Tau, and GABA in brain tissues, a very rapid and simple chromatographic method using high-performance liquid chromatography with electrochemical detection in combination with o-phthalaldehyde derivatization is described. Because the present method permits the determination of these five amino acids within less than five minutes in one chromatographic run, up to 100 samples a working day can be analyzed using an autosampler. Withinrun coefficients of variation for these five amino acids were less than 2% (n=20). The quantitative detection limit was 2.5 pmol for the 5 amino acids. The present method has been applied to the measurement of the five amino acid neurotransmitter levels in several discrete brain regions of mice treated with and without electroconvulsive shock.

MKC-231, a choline uptake enhancer, ameliorates working memory deficits and decreased hippocampal acetylcholine induced by ethylcholine aziridinium ion in mice

Abstract: The effects of acute and chronic administration of MKC-231, a new choline uptake enhancer, and two other nootropic agents, linopiridine (Dup 996) and tetrahydroaminoacridine (THA) on working memory deficits and decreased hippocampal acetylcholine (ACh) content were studied in a delayed non-matching to sample task, using a T-maze, in ethylcholine aziridinium ion (AF64A)-treated mice. Treatment with AF64A (3.5 nmol, i.c.v.) produced memory deficits and decreased hippocampal ACh content. In acute behavioral experiments, MKC-231 and THA had no significant effect on AF64A-induced memory deficits at any doses tested (0.3, 1.0 and 3.0 mg/kg), whereas Dup 996, at a dose of 1.0 mg/kg, significantly improved memory deficits. In chronic experiments, MKC-231 improved memory deficit at all doses tested (0.3, 1.0, or 3.0 mg/kg p.o., once daily for 11 days) and Dup 996 did so only at a dose of 3.0 mg/kg, whereas THA did not improve memory deficit at any doses tested. In acute neurochemical experiments, MKC-231 and THA did not reverse the AF64A-induced hippocampal ACh depletion. Dup 996, however, further decreased hippocampal ACh content compared to that in the AF64A-treated group. In chronic experiments, MKC-231 significantly reversed hippocampal ACh depletion at doses of 0.3 and 1.0 mg/kg, whereas neither Dup 996 nor THA reversed hippocampal ACh depletion at any doses tested. These results indicate that MKC-231 improved the AF64A-induced working memory deficit and hippocampal ACh depletion, probably by recovering reduced high-affinity choline uptake and ACh release.

Does Fast Dissociation From the Dopamine D2 Receptor Explain the Action of Atypical Antipsychotics?: A New Hypothesis

Abstract: OBJECTIVE: Although atypical antipsychotics are becoming the treatment of choice for schizophrenia, what makes an antipsychotic “atypical” is not clear. This article provides a new hypothesis about the mechanism of action of atypical antipsychotics. METHOD: Published data regarding the molecular, animal model, neuroimaging, and clinical aspects of typical and atypical antipsychotics were reviewed to develop this hypothesis. Particular attention was paid to data regarding the role of the serotonin 5-HT2 and dopamine D4 receptors in atypicality. RESULTS: Neuroimaging data show that optimal dopamine D2 occupancy is sufficient to produce the atypical antipsychotic effect. Freedom from motor side effects results from low D2 occupancy, not from high 5-HT2 occupancy. If D2 occupancy is excessive, atypicality is lost even in the presence of high 5-HT2 occupancy. Animal data show that a rapid dissociation from the D2 receptor at a molecular level produces the atypical antipsychotic effect. In vitro data show that ...

The neuropsychology of 3-D space

Abstract: The neuropsychological literature on 3-D spatial interactions is integrated using a model of 4 major behavioral realms: (a) peripersonal (visuomotor operations in near-body space), (b) focal extrapersonal (visual search and object recognition), (c) action extrapersonal (orienting in topographically defined space), and (d) ambient extrapersonal (orienting in earth-fixed space). Each is associated with a distinct cortical network: dorsolateral peripersonal, predominantly ventrolateral focal-extrapersonal, predominantly ventromedial action-extrapersonal, and predominantly dorsomedial ambient-extrapersonal systems. Interactions in 3-D space are also regulated neurochemically with dopaminergic and cholinergic excitation associated with extrapersonal activation and noradrenergic and serotonergic excitation associated with peripersonal activation. This model can help explain the 3-D imbalances in prominant neuropsychological disorders.

Role of dynorphin and enkephalin in the regulation of striatal output pathways and behavior.

Abstract: Projection neurons in the striatum give rise to two output systems, the "direct" and "indirect" pathways, which antagonistically regulate basal ganglia output. While all striatal projection neurons utilize GABA as their principal neurotransmitter, they express different opioid peptide co-transmitters and also different dopamine receptor subtypes. Neurons of the direct pathway express the peptide dynorphin and the D1 dopamine receptor, whereas indirect pathway neurons express the peptide enkephalin and the D2 receptor. In the present review, we summarize our findings on the function of dynorphin and enkephalin in these striatal output pathways. In these studies, we used D1- or D2-receptor-mediated induction of immediate-early genes as a cellular response in direct or indirect projection neurons, respectively, to investigate the role of these opioid peptides. Our results suggest that the specific function of dynorphin and enkephalin is to dampen excessive activation of these neurons by dopamine and other neurotransmitters. Levels of these opioid peptides are elevated by repeated, excessive activation of these pathways, which appears to be an adaptive or compensatory response. Behavioral consequences of increased opioid peptide function in striatal output pathways may include behavioral sensitization (dynorphin) and recovery of motor function (enkephalin).

The catalepsy test: its ups and downs.

Abstract: The typical catalepsy test consists of placing an animal into an unusual posture and recording the time taken to correct this posture. This time is regarded as an index of the intensity of catalepsy. Catalepsy is a robust behavior, and the lack of standardization does not usually hinder its actual detection. However, the intensity of the cataleptic effect is influenced by minor methodological differences, and thus interpretation and comparison of results across laboratories are difficult. The behavioral catalepsy test can use any of several different apparatus, including wire grids, parallel bars, platforms, or pegs, to situate the animals in unusual positions. The most common, however, is the "bar test," and despite its wide use in psychopharmacological research, even parameters of this test are not standardized. The present article reviews the wide variety of parameters chosen by investigators that measure catalepsy. The methodological issues of repeated testing, scaling of scores, apparatus, animal weight, maximal test duration, behavioral criteria, and other influences are discussed. In addition, a brief review of the neuropharmacological basis of catalepsy is also included. Finally, it is argued that a universal, standardized bar test be adopted by researchers. New data on a novel automated bar test in the Digiscan Activity Monitoring System is presented.