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Biomedical subjects

Minoru Tsuji

Publications and source records attributed to Minoru Tsuji.

11 recordsLinked to original sources
PubMed2006

Antidepressants enhance the antinociceptive effects of carbamazepine in the acetic acid-induced writhing test in mice.

Some antidepressants, as well as antiepileptics, are effective for treating pain of varying etiology. The present study was designed to characterize the antinociceptive effects of imipramine, a tricyclic antidepressant, fluvoxamine, a selective serotonin reuptake inhibitor, milnacipran, a serotonin noradrenaline reuptake inhibitor, and carbamazepine, an antiepileptic drug, using the acetic acid-induced writhing test in mice. Imipramine (1.25-10 mg/kg, i.p.), fluvoxamine (5-40 mg/kg, i.p.) and milnacipran (2.5-20 mg/kg, i.p.) all dose-dependently and significantly reduced the number of writhes induced by the injection of acetic acid (0.8% (v/v)), although the maximal effect of milnacipran was weaker than those of imipramine and fluvoxamine. Similarly, carbamazepine (5-20 mg/kg, i.p.) also showed a dose-dependent and significant antinociceptive effect. In combination studies, the co-administration of a sub-effective dose of carbamazepine (5 mg/kg, i.p.) with imipramine (1.25 and 2.5 mg/kg, i.p.), fluvoxamine (10 mg/kg, i.p.) or milnacipran (1.25 and 2.5 mg/kg, i.p.) significantly reduced the number of writhes. Additionally, the hole-board test revealed that the medications with significant antinociceptive effects barely produced changes in motor activity that could possibly affect writhing behavior. Thus, the present study demonstrated that the antinociceptive effect of carbamazepine is enhanced by combination with imipramine, fluvoxamine and milnacipran. Therefore, the combined therapy using antidepressants and carbamazepine may be useful clinically for the control of pain.

Acetic Acid↗
PubMed2006

Caffeic acid attenuates the decrease in cortical BDNF mRNA expression induced by exposure to forced swimming stress in mice.

We previously reported that caffeic acid produces antidepressive-like effects in the forced swimming test in mice, an animal model of depression. Increased evidence suggests that brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family that has high affinity for the tyrosine kinase receptor B (TrkB), plays an important role in the pathophysiology and treatment of depression. The present study examined whether caffeic acid affects the expression levels of BDNF and TrkB mRNA in brain regions of mice subjected to a forced swimming test. Caffeic acid (4 mg/kg, i.p.) reduced the duration of immobility of mice in the forced swimming test. The levels of BDNF mRNA in the frontal cortex as well as TrkB mRNA in the amygdala were significantly decreased after the forced swimming test, and the former reduction was significantly inhibited by caffeic acid (4 mg/kg, i.p.). Caffeic acid (4 mg/kg, i.p.) did not modify the levels of BDNF and TrkB mRNA in brain regions of naive mice. These results suggest that caffeic acid can attenuate the down-regulation of BDNF transcription that results from stressful conditions.

Animals↗
PubMed2005

Effects of a 5-HT7 receptor antagonist DR4004 on the exploratory behavior in a novel environment and on brain monoamine dynamics in mice.

The present study examined whether serotonin (5-hydroxytryptamine; 5-HT)7 receptors play a role in the modulation of emotionality in mice using the selective 5-HT7 receptor antagonist 2a-[4-(4-phenyl-1,2,3,6-tetrahydropyridyl)butyl]-2a,3,4,5-tetrahydrobenzo (c,d)indol-2-(1H)-one (DR4004). The emotionality of mice was evaluated in terms of exploratory activity in the hole-board test. The mice treated with DR4004 (2.5-10 mg/kg, i.p.) displayed a dose-dependent decrease in locomotor activity by moving less distance in the hole-board, and statistically significant decreases were observed at 5 and 10 mg/kg. On the other hand, DR4004 (10 mg/kg, i.p.) did not affect spontaneous motor activity. In a neurochemical study, decreases in amygdaloid dopamine and 5-HT turnover were observed in mice in which locomotor activity in the hole-board test was attenuated following the administration of DR4004 (10 mg/kg, i.p.). Also, a simple linear regression analysis revealed that locomotor activity on the hole-board was significantly correlated with dopamine and 5-HT turnover in amygdala. Furthermore, co-injection of the selective dopamine reuptake inhibitor 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)piperazine (GBR12909; 1.25-5 mg/kg, i.p.) or the selective 5-HT reuptake inhibitor fluvoxamine (20 mg/kg, i.p.) significantly reversed the DR4004 (10 mg/kg, i.p.)-induced decrease in locomotor activity in the hole-board test. These findings constitute the behavioral evidence that 5-HT7 receptors may play a role in the modulation of emotionality. Furthermore, it is also suggested that amygdaloid dopamine and 5-HT neuronal systems may be involved in this modulation.

Amygdala↗
PubMed2004

Characterization of the anxiolytic-like effects of fluvoxamine, milnacipran and risperidone in mice using the conditioned fear stress paradigm.

It has been known that rodents exhibit the immobility when tested in the same environment in which they had been previously exposed to aversive stimuli. This behavior is called conditioned fear stress-induced freezing behavior, and has been used as a model of anxiety. Using this animal model, the present study tried to characterize the anxiolytic-like effects of fluvoxamine, a selective serotonin reuptake inhibitor, milnacipran, a serotonin noradrenaline reuptake inhibitor and risperidone, an atypical antipsychotic in mice. Fluvoxamine (1.25-10 mg/kg, intraperitoneally (i.p.)) and milnacipran (0.5-4 mg/kg, i.p.) each dose-dependently and significantly suppressed the conditioned fear stress-induced freezing behavior in mice, an indicator of anxiety, and milnacipran had a weaker effect than fluvoxamine. While risperidone also significantly suppressed freezing behavior at a low dose (0.01 mg/kg, i.p.), a high dose (0.04 mg/kg, i.p.) decreased spontaneous motor activity. On the contrary, sulpiride, a typical antipsychotic (2-8 mg/kg, i.p.), did not affect freezing behavior. In a combination study, the suppressive effect of a low dose of risperidone (0.01 mg/kg, i.p.) on freezing behavior was significantly antagonized by the co-administration of low/middle doses of fluvoxamine (1.25 and 2.5 mg/kg, i.p.), whereas a high dose of fluvoxamine (10 mg/kg, i.p.) was unaffected. Additionally, the co-administration of milnacipran (0.5-2 mg/kg, i.p.) also tended to inhibit the suppressive effect of risperidone (0.01 mg/kg, i.p.). These findings indicate that fluvoxamine, milnacipran and risperidone may each be clinically effective at treating anxiety disorders, but their effects may be attenuated in combination with other medications.

Animals↗
PubMed2003

Caffeic acid produces antidepressive- and/or anxiolytic-like effects through indirect modulation of the alpha 1A-adrenoceptor system in mice.

We previously reported that caffeic acid produce antidepressive- and/or anxiolytic-like effects in two different types of stress models. It has recently been reported that caffeic acid affects the alpha1A-adrenoceptor system. The present study examined whether the alpha1A-adrenoceptor system is involved in the antidepressive- and/or anxiolytic-like effects of caffeic acid. Caffeic acid reduced the duration of immobility and freezing of mice produced by forced swimming and conditioned fear stress, respectively. These effects of caffeic acid were suppressed by the alpha1- and alpha1A-adrenoceptor antagonists. However, caffeic acid did not alter the binding of [3H]prazosin to alpha1A-adrenoceptor in mouse cortical membranes. These results suggest that indirect modulation of the alpha1A-adrenoceptor system may be involved in the antidepressive- and/or anxiolytic-like effects of caffeic acid.

Animals↗
PubMed2003

Pathophysiologic characteristics of the activity-stress paradigm in animal models: inhibitory effect of glucose on these responses.

This review provides a discussion of the pathophysiologic significance of animal models of the activity-stress paradigm and the role of plasma glucose level in the appearance of physical stress responses of those models. Many research reports have demonstrated that animal models exposed to activity-stress are useful as a "symptomatic model" of anorexia nervosa and obsessive-compulsive disorder as well as peptic ulcer. Our findings show that a decrease in plasma glucose concentration is an important factor in determining the activity-stress-induced physical responses. Further investigation of the pathophysiology of activity-stressed animal models may contribute to the development of new therapeutics for diseases such as anorexia nervosa and obsessive-compulsive disorder.

Animals↗
PubMed2002

Modulation of passive avoidance in mice by the 5-HT1A receptor agonist flesinoxan: comparison with the benzodiazepine receptor agonist diazepam.

The effects of the 5-HT(1A) receptor agonist flesinoxan on passive avoidance in mice were compared with those of the benzodiazepine receptor agonist diazepam. In preliminary experiments, the retention latency to enter a dark compartment in mice subjected to single-training sessions with 0.6-mA electric foot shocks for 4, 8, or 16 s slightly increased in all of the test sessions (immediately, 24 h, and 1 week after the training sessions), but none of these changes were significant. In contrast, mice subjected to double-training sessions with 0.6-mA electric foot shocks for 16 s showed a significant increase in retention latency in all of the test sessions. Pretreatment with either flesinoxan or diazepam 30 min before the double-training sessions with 0.6-mA electric foot shocks for 16 s significantly decreased the retention latency in test sessions 24 h and 1 week later. In contrast, mice pretreated with flesinoxan 24 h before the single-training sessions with 0.6-mA electric foot shocks for 4, 8, or 16 s showed a significant increase in retention latency in the test sessions 24 h and/or 1 week later. Similar enhancements of retention latency in the test sessions 24 h and/or 1 week later were observed also in mice pretreated with flesinoxan 24 h before the double-training sessions. However, in this time interval following injection, pretreatment with diazepam did not affect the retention latency of mice in any of the test sessions. Neither flesinoxan nor diazepam, at the same doses and time intervals used in the passive avoidance study, modified the thresholds for flinching and jumping elicited by electrical stimuli. These results suggest that the activation of 5-HT(1A) receptors, but not benzodiazepine receptors, has a dual effect on the formation of learning and memory for an aversive event that depends on the time interval following receptor activation.

Animals↗
PubMed2002

Rosmarinic acid and caffeic acid reduce the defensive freezing behavior of mice exposed to conditioned fear stress.

RATIONALE: We previously showed that rosmarinic acid from the leaves of Perilla frutescens Britton var. acuta Kudo (Perillae Herba) and its major metabolite caffeic acid have antidepressive-like activity in the forced swimming test. OBJECTIVE: The present study was designed to examine whether rosmarinic acid and caffeic acid might also be effective in other types of stress model. METHODS: The conditioned fear stress paradigm was used as a stress model for assessing the effects of rosmarinic acid and caffeic acid. RESULTS: Rosmarinic acid (0.25-4 mg/kg, IP) induced a dose-dependent, U-shaped reduction in the duration of the defensive freezing behavior of mice exposed to conditioned fear stress. Caffeic acid (1-8 mg/kg, IP) also dose-dependently reduced this freezing behavior. However, neither substance, at doses that produced a significant reduction in the freezing behavior, affected spontaneous motor activity. CONCLUSIONS: These results confirm that rosmarinic acid and caffeic acid may inhibit the emotional abnormality produced by stress.

Analysis of Variance↗
PubMed2002

Rosmarinic acid and caffeic acid produce antidepressive-like effect in the forced swimming test in mice.

We previously showed that rosmarinic acid from the leaves of Perilla frutescens Britton var. acuta Kudo (Perillae Herba) has antidepressive-like activity. The aim of the present study was to examine (i) whether caffeic acid, a major metabolite of rosmarinic acid, also has antidepressive-like activity, and (ii) whether these substances inhibit either the uptake of monoamines to synaptosomes or mitochondrial monoamine oxidase activity. Rosmarinic acid (2 mg/kg, i.p.) and caffeic acid (4 mg/kg, i.p.) each significantly reduced the duration of immobility in the forced swimming test in mice. In contrast, neither substance, at doses that produced a significant reduction in the immobile response in the forced swimming test, affected spontaneous motor activity. These results indicate that, like rosmarinic acid, caffeic acid also possesses antidepressive-like activity. In neuropharmacological studies, neither rosmarinic acid (10 x (-9)-10 x (-3) M) nor caffeic acid (10 x (-9)-10 x (-3) M) affected either the uptake of monoamines to synaptosomes or mitochondrial monoamine oxidase activity in the mouse brain. These results suggest that both caffeic acid and rosmarinic acid may produce antidepressive-like activity via some mechanism(s) other than the inhibition of monoamine transporters and monoamine oxidase.

Animals↗
PubMed2002

Identification of rosmarinic acid as a novel antidepressive substance in the leaves of Perilla frutescens Britton var. acuta Kudo (Perillae Herba).

The leaves of Perilla frutescens Britton var. acuta Kudo (Perillae Herba) are found in some traditional oriental herbal medicines that are primarily used to treat affective disorders such as depression and anxiety. The aim of the present study was to identify the bioactive component in Perillae Herba that possesses antidepressive activity. The effects of a water extract of Perillae Herba and six fractions therefrom were evaluated in mice by use of the forced-swimming test. An oral administration of a water extract of Perillae Herba significantly reduced the duration of immobility. Moreover, 50% methanol extract of the water extract of Perillae Herba and its 30% methanol extract also reduced the duration of immobility. Three-dimensional high-performance liquid chromatography and FAB-MS and NMR spectral analysis clearly showed that the extracts with anti-immobility effects contained abundant rosmarinic acid. The oral and intraperitoneal administration of rosmarinic acid significantly reduced the duration of immobility. In contrast, a water extract from another species of Perillae Herba, which contains only low levels of rosmarinic acid, had no anti-immobility effect. These results suggest that rosmarinic acid may be the main component involved in the antidepressive effect of Perillae Herba in the forced-swimming test. Thus it may be a novel antidepressive substance.

Animals↗