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Biomedical subjects

M Toru

Publications and source records attributed to M Toru.

At least 91 records · Page 5Linked to original sources

Effect of a single injection of psychoactive drugs on CCK mRNA in rat brain.

The acute and long-term effects of a single injection of psychoactive drugs, methamphetamine or phencyclidine, were investigated by Northern blot to assess alterations in the cholecystokinin (CCK) mRNA in three areas of the rat brain. In the frontal cortex, there were no significant changes in CCK mRNA after the drug injection. In contrast, decreases in CCK mRNA were observed in the posterior cortex and the hippocampus from 30 min to 48 h after the drug treatment. The data suggest that CCK gene expression has different sensitivity to these psychoactive drugs within the cortices.

Animals↗

Lower interhemispheric coherence in a case of agenesis of the corpus callosum.

Interhemispheric coherence and relative power were compared in a patient with total agenesis of the corpus callosum and age and sex matched controls. The patient showed lower interhemispheric coherence than normal controls in F3-F4, C3-C4, and in P3-P4 especially in the higher theta, lower alpha, and beta bands. Differences in relative power were much less marked. These results seem to reflect that interhemispheric connection is degraded because of callosal agenesis.

Adolescent↗

Modulation of [3H]mazindol binding sites in rat striatum by dopaminergic agents.

This study was undertaken to examine whether repeated alteration of dopamine turnover influences the function of dopamine uptake sites. In the first experiment, rats were repeatedly injected intraperitoneally with L-3,4-dihydroxyphenylalanine (L-DOPA), alpha-methyl-p-tyrosine or 1-[2-bis(4-fluorophenyl)methoxy]ethyl]-4-(3- phenylpropyl)piperazine (GBR 12909) once daily for 14 days. An increase in the number of [3H]mazindol binding sites in the striatum was seen with L-DOPA and GBR 12909. A decrease was seen with alpha-methyl-p-tyrosine. In the second experiment, the effect of a single treatment with the same drugs was investigated and no change in the number and affinity of [3H]mazindol binding sites was found. These results indicate that the number of dopamine uptake sites is modulated by persistent changes in dopamine turnover, and that repeated treatment with a selective dopamine uptake inhibitor, GBR 12909, increases their number.

3,4-Dihydroxyphenylacetic Acid↗

A structural polymorphism of human dopamine D2 receptor, D2(Ser311-->Cys).

No structural change of the dopamine D2 receptor (DRD2) has been reported so far, though the DRD2 gene has been suggested to be one of the candidate genes for mental disorders. Herein we report one missense nucleotide mutation from C to G resulting in a substitution of serine with cystein at the codon 311 located in the third intracellular loop of the DRD2 that was found in the analyses of the sequence of the DRD2 gene in 50 schizophrenics. The allele frequency, 0.04, of this Cys311 allele in 50 schizophrenics was slightly increased compared with that, 0.023, in 110 controls though the difference was not significant. The schizophrenics with Cys311 tended to have a lower age of onset and a positive family history of schizophrenia.

Alleles↗

Association between severity of alcoholism and the A1 allele of the dopamine D2 receptor gene TaqI A RFLP in Japanese.

The allelic association of TaqI A restriction fragment length polymorphism (RFLP) of the dopamine D2 receptor gene with alcoholism was examined in 78 Japanese alcoholics and compared with Japanese controls. A significantly higher frequency of the A1 allele (0.42) was found in 100 Japanese unscreened controls compared with those reported in white populations. Among 70 alcoholics whose severities were determined, the A1 allele was present in 77% of 43 more severe alcoholics and in 59% of 27 less severe alcoholics. The A1 allele was present significantly less frequently in the alcoholics at the age of 60 or older (42%), compared with those under the age of 60 (74%). In the subjects under the age of 60, the A1 allele was present in 83% of the 35 more severe alcoholics, being significantly more frequent than in 60% of the 35 nonalcoholic controls. All of the 7 alcoholics homozygous for the A1 allele were classified as severe. The average severity of alcoholism increased in the order A2/A2, A1/A2, and A1/A1 genotypes. These data suggest that the A1 allele is associated with severe alcoholism in the Japanese population and that the effect is related to or has a linkage disequilibrium with a genetic factor that has a small but not negligible additive effect on alcoholism.

Age Factors↗

Involvement of the fimbria fornix in the initiation but not in the expression of methamphetamine-induced sensitization.

To put forward our previous finding that the lesion of the fimbria fornix, a hippocampo-accumbal pathway, blocked the development of behavioral sensitization induced by repeated methamphetamine (MAP) administrations, we examined the role of the fimbria fornix in the expression of sensitization in this study. After rats had shown locomotor augmentation following repeated drug injections, they received either the fimbria fornix lesion or a sham operation. Both groups of rats still exhibited a similar sensitized locomotor response to MAP as before the surgeries. In addition, we evaluated dopamine metabolism in the nucleus accumbens of these rats following a challenge injection of MAP after the behavioral study. The data obtained correspond to the results of behavioral experiments in that 3-methoxytyramine, one of the dopamine metabolites, increased significantly after MAP challenge only in the groups of sensitized animals. These findings further support the recent concept that there may exist different neural mechanisms in the initiation and expression of sensitization phenomenon.

3,4-Dihydroxyphenylacetic Acid↗

Measurement of glutamate, aspartate and glycine and its potential precursors in human brain using high-performance liquid chromatography by pre-column derivatization with dimethylaminoazobenzene [correction of diethylaminoazobenzene] sulphonyl chloride.

This paper describes a high-performance liquid chromatographic technique, with dimethylaminoazobenzene sulphonyl chloride derivatization, for the measurement of glutamate, aspartate and glycine and its potential precursors in human brain tissue. The derivatization procedure is simple, sensitive and highly reproducible. The derivatized amino acids are stable and can be analysed by reversed-phase chromatography with visible detection at an absorption wavelength of 436 nm. A preliminary application to the determination of the concentrations of several amino acids in several regions of the human brain is described.

Aged↗

EEG coherence in unmedicated schizophrenic patients: topographical study of predominantly never medicated cases.

Electroencephalographic (EEG) power and coherence were compared in 11 unmedicated schizophrenics (including 9 never mediated patients) and in 15 normal controls. There was no significant difference in power between the two groups. However, interhemispheric coherence between O1-O2 was higher in the schizophrenics in the delta and beta bands, and interhemispheric coherence between T5-T6 was higher in the delta band. These results suggest that coherence is more sensitive than power for comparison of these two groups, and that cerebral function is less lateralized in schizophrenics.

Adult↗

Sigma receptors in schizophrenic cerebral cortices.

Antipsychotics represent high affinity for sigma receptors and sigma-like drugs often have the psychotomimetic properties. Besides, the receptors are unevenly distributed in human brain. These findings suggest that sigma receptors might be involved in the pathophysiology of schizophrenia. Sigma receptors in rat and human brain were measured with [3H]-1, 3, di-o-tolylguanidine (DTG) and non-specific binding of [3H]DTG was determined in the presence of 10(-5)M haloperidol. Monovalent and divalent cations strongly inhibited [3H]DTG binding. Glutamate, aspartate and glycine also decreased the binding to human cerebral membranes. With post-mortem brain samples from 12 schizophrenics and 10 controls, sigma receptors were measured in 17 areas of cerebral cortex. Sigma receptors binding showed the regional differences in the cortex, but no significant differences between schizophrenics and controls were observed except the superior parietal cortex where the binding significantly increased in the schizophrenic group. These results suggest that sigma receptors in cerebral cortices might not be directly concerned with the pathophysiological role in schizophrenia.

Adult↗

Alpha-[3H]amino-3-hydroxy-5-methylisoxazole-4-propionic acid binding to human cerebral cortical membranes: minimal changes in postmortem brains of chronic schizophrenics.

The binding of alpha-[3H]amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]AMPA), a selective ligand for the ion channel-linked quisqualate receptor, was evaluated in Triton X-100-treated membranes of human cerebral cortex. The presence of chaotropic ions produced divergent effects on specific [3H]AMPA binding: A twofold increase in the binding was observed with thiocyanide at 100 mM, although iodide (100 mM) and perchlorate (100 mM) reduced the binding. Chemical modifications of the sulfhydryl group with p-chloromercuriphenylsulfonic acid (PCMBS) produced threefold increases in specific [3H]-AMPA binding in the absence of KSCN as well as in the presence of KSCN. Treatment with dithiothreitol restored the enhanced specific [3H]AMPA binding by PCMBS to the basal level. Although specific [3H]AMPA binding in the absence of KSCN showed a single site (KD = 220 nM, Bmax = 235 fmol/mg of protein), curvilinear Scatchard plots of specific [3H]AMPA binding in the presence of 100 mM KSCN can be resolved into two binding sites with the following parameters: KD1 = 5.82 nM, Bmax1 = 247 fmol/mg of protein; KD2 = 214 nM, Bmax2 = 424 fmol/mg of protein. Quisqualate and AMPA were the most potent inhibitors of the [3H]AMPA binding in the presence of KSCN. Potent inhibitors of the binding included beta-N-oxalylamino-L-alanine (L-BOAA), cysteine-S-sulfate, L-glutamate, 6-cyano-7-nitroquinoxaline-2,3-dione, and 6,7-dinitroquinoxaline-2,3-dione. Kainate, L-homocysteine sulfinic acid, and L-homocysteic acid were active with an IC50 value of a micromolar concentration, whereas L-cysteic acid and L-cysteine sulfinic acid were weakly active.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Chloromercuribenzenesulfonate↗

Effects of sulpiride and oxypertine on the dopaminergic system in the rat striatum.

We have examined the effects of sulpiride, oxypertine and haloperidol on the behavioral and biochemical dopamine receptor function in the rat striatum. Although acute treatment with haloperidol or oxypertine induced catalepsy, tolerance to catalepsy developed following chronic treatment with haloperidol but not with oxypertine. Rats treated with acute or chronic sulpiride did not show signs of catalepsy. Intracerebroventricular administration of sulpiride, however, induced catalepsy and tolerance developed after chronic treatment. After chronic treatment with either of these three drugs, dopamine D2 receptors were up-regulated in the striatum. While acute administration of haloperidol, sulpiride or oxypertine increased the concentration of homovanillic acid in the striatum, the rate of increases was attenuated following chronic treatment with haloperidol or sulpiride, but not with oxypertine. While acute administration of sulpiride or oxypertine decreased dopamine, the decrease was attenuated following repeated administration of sulpiride but not of oxypertine. These results suggest that the unique pharmacological profile of oxypertine may be related to its therapeutic effect of activating apathetic patients, and that both sulpiride and oxypertine may cause tardive dyskinesia, as haloperidol does.

Animals↗

Blockade of behavioral sensitization to methamphetamine by lesion of hippocampo-accumbal pathway.

The present studies were carried out to explore a role of the hippocampal efferents in the development of the locomotor augmentation induced by repeated methamphetamine administrations. For this purpose, electrolytic lesions of either the dorsal fornix or the fimbria fornix were made bilaterally in rats. The latter treatment, not the former, blocked the behavioral sensitization. These results suggest that the hippocampo-accumbal pathway may play an important role in the development of the sensitization.

Animals↗