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Biomedical subjects

S Ueki

Publications and source records attributed to S Ueki.

At least 55 records · Page 3Linked to original sources
PubMed1992

Protective effect of minaprine against the abnormal changes of 2-deoxyglucose uptake by rat hippocampal slices induced by hypoxia/hypoglycemia.

Effect of minaprine on hypoxia- or hypoxia/hypoglycemia (ischemia)-induced impairment of 2-deoxyglucose (2DG) uptake by rat hippocampal slices was evaluated. Since minaprine was found to possess both a stimulating effect on acetylcholine release and a blocking effect on 5-HT2 receptors, the improving effect of minaprine on impaired 2DG uptake was compared to the findings obtained with oxotremorine, ketanserin and pentobarbital. Hippocampal slices were exposed to 20-min ischemia, and then these slices were returned to oxygenated and glucose-containing buffer for 6 hr. Ischemia reduced 30 mM KCl-induced 2DG uptake by the hippocampus. Pretreatment with minaprine, oxotremorine, pentobarbital and ketanserin attenuated the ischemia-induced decline of 2DG uptake. In addition, minaprine, oxotremorine and pentobarbital relatively recovered the increase of 2DG uptake in the hippocampal slices under hypoxia for 45 min. The present results suggest that minaprine exerts a neuroprotective action against ischemia-induced deficit of energy metabolism in vitro.

Acetylcholine↗
PubMed1991

Effect of the kappa-receptor agonist, U-50,488H, on cerebral ischemia-induced impairment of working memory assessed in rats by a three-panel runway task.

The effect of U-50,488H, a selective kappa-receptor agonist, on memory functions in an animal model of cerebral ischemia was investigated by use of a three-panel runway task. A 5-min period of ischemia caused a significant increase in the number of errors (pushes made on the two incorrect panels of the three panel-gates at four choice points) in a working memory task but it did not impair a reference memory task. U-50,488H at 10 and 32 mg/kg, administered i.p. immediately after blood flow restoration significantly reduced the increase in errors expected to occur in a working memory task assessed 24 h after 5 min of ischemia. This protective effect of U-50,488H on amnesia in the ischemic rat was antagonized by the kappa-receptor antagonist, MR-2266. We conclude that U-50,488H prevents the impairment of working memory following transient forebrain ischemia, an event mediated by the activation of the kappa-opioid receptor.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1991

Pharmacological profile of a potential anxiolytic: AP159, a new benzothieno-pyridine derivative.

AP159 [N-cyclohexyl-1,2,3,4-tetrahydrobenzo(b)thieno(2,3c)pyridine]-3- carboamide,hydrochloride) showed clear anti-conflict activity in rats in the absence of effects on muscle relaxation, potentiation of anesthesia (in mice) or anticonvulsant activity (in mice). This anti-conflict effect was antagonized by treatment with Ro15-1788. By contrast with the deficits produced by diazepam, AP159 did not impair passive avoidance. The latter drug also improved scopolamine-induced amnesia in the same task. AP159 did not inhibit 3H-flunitrazepam binding, but potently inhibited 3H-8OH-DPAT binding. This compound increased serotonin and 5HIAA content of the midbrain raphe nuclei and of the amygdala centralis. AP159 has been shown to be a novel non-BZP anxiolytic agent with no side effects in laboratory animals; it could be a clinically effective anxiolytic agent.

Aggression↗
PubMed1991

Involvement of the dorsal hippocampus in mediation of the antianxiety action of tandospirone, a 5-hydroxytryptamine1A agonistic anxiolytic.

The effect of tandospirone, a 5-hydroxytryptamine (5-HT)1A agonist/anxiolytic, injected directly into dorsal hippocampus, on Vogel-type conflict behavior in rats was investigated and the findings were compared with the effects of diazepam and zopiclone. Tandospirone (30 micrograms/2 microliters and 60 micrograms/2 microliters) and diazepam (40 micrograms/2 microliters) but not zopiclone (20 micrograms/2 microliters), produced a potent anticonflict action in rats. The anticonflict action of tandospirone (30 micrograms/2 microliters), injected into the dorsal hippocampus, was significantly blocked by (-)-propranolol (5 mg/kg i.p.). The present findings provide evidence that suggests that tandospirone has an antianxiety action, presumably by stimulating 5-HT1A receptors in the dorsal hippocampus.

Animals↗
PubMed1991

Cardiovascular changes induced by chemical stimulation of the amygdala in rats.

The role of the amygdaloid complex in the central regulation of the cardiovascular system was studied in unanesthetized, unrestrained rat. The injection of carbachol into the amygdaloid complex elicited a pressor response, whereas the injection of noradrenaline and 5-hydroxytryptamine into the same area caused no significant cardiovascular changes. The greatest pressor response was obtained when carbachol was injected into the central nucleus. Bradycardia and tachycardia occurred when injection of carbachol was made into dorso-central and medio-ventral parts of the amygdaloid complex, respectively. Concomitant with cardiovascular responses, the injection of carbachol into the amygdaloid complex produced behavioral changes including immobilization, body shaking, searching and rearing. The pressor response and bradycardia were suppressed by prior local injection into the amygdaloid complex of atropine but not hexamethonium. These results suggest that the cholinergic system mediated by activation of muscarinic receptors in the amygdaloid complex may play a role in the control of cardiovascular and autonomic function.

Amygdala↗
PubMed1991

[Behavioral pharmacological and electroencephalographic effects of the 5-HT1A partial agonist ipsapirone].

The behavioral and EEG effects of the 5-HT1A partial agonist ipsapirone were investigated to determine its pharmacological characteristics as an anxiolytic drug in rats, mice and rabbits, as compared with those of buspirone and diazepam. 1) The anticonflict effect of ipsapirone was almost equipotent as that of buspirone and less potent than that of diazepam in rats. Ro15-1788 antagonized the anticonflict effect of diazepam, but did not that of ipsapirone. 2) Muricide in midbrain raphe-lesioned and olfactory bulbectomized rats was inhibited by ipsapirone. However, the inhibition of muricide by ipsapirone was attenuated by its repeated administration. 3) The muscle relaxant effects of ipsapirone and buspirone on rotarod performance were less potent than that of diazepam. Ethanol-induced muscle relaxation was markedly potentiated by diazepam, but less potently by ipsapirone and buspirone. 4) The pentetrazol-induced convulsion was dose-dependently antagonized by diazepam, while it was weakly potentiated by ipsapirone and buspirone. 5) The limbic afterdischarges induced by either hippocampal or amygdaloid stimulation in rabbits were markedly inhibited by diazepam. Conversely, ipsapirone and buspirone slightly potentiated afterdischarges. In conclusion, it is suggested that ipsapirone has anxiolytic activities similar to that of buspirone and moderate antimuricidal action. In addition, ipsapirone, like buspirone, is also characterized by its less potent muscle relaxant, alcohol-potentiating and anticonvulsant actions.

Animals↗
PubMed1991

Effects of successive doses of nizatidine, cimetidine and ranitidine on serum gastrin level and gastric acid secretion.

Nizatidine (N-[2-[[[2-[(dimethylamino)methyl]- 4-thiazolyl]methyl]thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine , CAS 76963-41-2) is a new histamine H2-receptor antagonist which shows suppression of gastric acid secretion and antiulcer activity. In the present experiment, the effects of single s.c. administration of nizatidine, cimetidine and ranitidine on serum gastrin levels were studied in fasted rats. Nizatidine at 100 mg/kg increased serum gastrin level 3 h after administration, which however, returned to basal level 6 h after administration. Cimetidine and ranitidine at respective doses of 250 and 100 mg/kg markedly increased serum gastrin levels 3 and 6 h after administration. In a previous study, the suppressive effect of nizatidine on basal gastric acid secretion was 82.8% at a dose of 100 mg/kg s.c. in rat pylrus-ligated model. On the basis of these findings, changes in basal gastric acid secretion and serum gastrin level after withdrawal of nizatidine, cimetidine and ranitidine administered for 14 consecutive days were studied. One day after withdrawal, nizatidine at 100 mg/kg showed a tendency to increase the basal gastric acid secretion. However, 3 and 7 days after administration, almost no changes were obtained. Cimetidine at 250 mg/kg showed a tendency to increase the basal gastric acid secretion 7 days after withdrawal of the drug. Ranitidine at 100 mg/kg induced no changes in basal gastric acid secretion after withdrawal. No obvious influences of all drugs on serum gastrin level after withdrawals were obtained. These results indicate that consecutive administration of nizatidine may cause only a transient increase of gastric acid secretion but no hypergastrinaemia after its withdrawal.

Animals↗
PubMed1991

Development of skill of children in the performance of the family computer game "Super Mario Brothers".

The development of skill of children in the performance of a family computer game (Super Mario Brothers) was investigated among three groups of different age: kindergarten children (6 years old) and primary school children (9 and 12 years old). The skill to perform the game with either hand was evaluated by the mean scores gained by the children. In the normal (right and dominant) situation, the mean score improved significantly with advancement of age. Similar was true in the reversed (left hand dominant) situation, but more distinctly. The mean scores were significantly higher in the normal than in the reversed situations. The experienced children were superior to the inexperienced children in playing the game. The correlation between the reaction time and the game score was also investigated with the same subjects for the 9- and 12-year-old school children. Almost no correlation could be elucidated.

Age Factors↗
PubMed1990

Minaprine improves impairment of working memory induced by scopolamine and cerebral ischemia in rats.

Using a repeated acquisition procedure in a three-panel runway apparatus, the effects of minaprine on the impairment of working memory produced by scopolamine, ethylcholine aziridinium ion (AF64A) or cerebral ischemia were investigated in rats. Minaprine (3.2-32 mg/kg IP) as well as idebenone (10-100 mg/kg IP) and physostigmine (0.1-0.32 mg/kg IP) dose-dependently reduced the increase of errors (pushes made on the two incorrect panels located at each choice point) induced by 0.56 mg/kg IP scopolamine. Cerebral ischemia for 5 min caused a significant increase of errors in the runway task. Minaprine at 3.2 and 10 mg/kg administered IP immediately after blood recirculation and again 30 min before the runway test conducted 24 h after ischemia, significantly reduced increases in errors expected to occur after 5 min of ischemia. Physostigmine 0.1 mg/kg similarly attenuated the increase in errors in ischemic rats. However, minaprine at doses up to 32 mg/kg IP failed to reduce the increase of errors induced by AF64A 2.5 nmol injected into the dorsal hippocampus. These findings suggest that minaprine exerts an ameliorating effect on amnesia produced by scopolamine and cerebral ischemia, probably through mediation of its stimulant action on central cholinergic systems.

Animals↗
PubMed1990

Effects of GABA and anxiolytics on the single unit discharge of suprachiasmatic neurons in rat hypothalamic slices.

The effects of gamma-aminobutyric acid (GABA), muscimol, baclofen and the anxiolytics; diazepam (DZP), flurazepam (FZP) and zopiclone on single-unit neural activities in the suprachiasmatic nucleus (SCN) were investigated using the rat hypothalamic slice preparation. Exposure of the slice to GABA 10(-4) M produced inhibitory responses in 65% of the 49 SCN neurons examined. The threshold concentration of GABA ranged from 10(-6) to 10(-4) M. Neurons responsive to GABA were not found to be restricted to a subdivision of the SCN, but were diffusely distributed throughout the nucleus. DZP, FZP and zopiclone produced responses similar to those of GABA. The inhibitory effects of GABA (10(-5) M) were potentiated by coadministration of DZP (10(-5) M). Muscimol and baclofen (10(-7) M to 10(-4) M) also inhibited SCN neuronal activity in a dose-dependent manner. Bicuculline (10(-5) M-10(-4) M) scarcely affected the baclofen-induced inhibition (1/6) but strongly antagonized the effects of muscimol (6/6), GABA (6/8) and DZP (4/5). These results suggest that the receptors mediating the inhibitory effects of GABA and anxiolytics within the SCN may be GABAA and/or GABAB or GABA-BDZ receptor complex, respectively.

Animals↗
PubMed1990

[Studies on anti-ulcer effects of a new compound, zinc L-carnosine (Z-103)].

We investigated the anti-ulcer effects of zinc L-carnosine (Z-103) using several acute experimental models of gastric and duodenal lesions in rats. Effects of Z-103 on various gastric functions, e.g., antacid (in vitro), anti-pepsin (in vitro), gastric secretion, mucosal potential difference (PD) and mucus contents were also examined. Z-103 given orally prevented development of gastric lesions induced by water immersion stress, histamine, HCl-aspirin, HCl-ethanol and also duodenal ulcers induced by mepirizole in a dose-dependent manner. In vitro, Z-103 had a greater antacid effect than sodium bicarbonate; and moreover, the potency of its anti-peptic action (IC50 = 8.7 mM) was higher than those of several other drugs (sodium bicarbonate, sucrose sulfate and aceglutamide aluminum). Intragastric treatment of Z-103 (100 mg/kg alone tended to increase PD, and it also significantly inhibited the decrease in PD induced by aspirin. In addition, pretreatment with Z-103 at 10 and 30 mg/kg (p.o.) significantly prevented the decrease in mucus contents in the gastric mucosa and also mucosal lesions by oral administration of ethanol. On the other hand, Z-103 was not so effective on both basal (pylorus-ligation preparation) and histamine-stimulated gastric secretion (Heidenhain pouch preparation). These results suggest that Z-103 is useful for the treatment of gastric and duodenal ulcers in humans.

Animals↗
PubMed1990

beta-CCM inhibits muricide induced by olfactory bulbectomy in rats.

Intravenous administration of beta-CCM (methyl-beta-carboline-3-carboxylate) at doses ranging from 0.3 to 10 mg/kg dose-dependently inhibited muricide in olfactory bulbectomized rats. beta-CCM elicited a decrease of locomotor activity at doses ranging from 0.3 to 3 mg/kg, and it impaired rotarod performance at doses of 1 and 3 mg/kg. The inhibition of muricide induced by beta-CCM was antagonized by intraperitoneal administration of Ro15-1788 at 10 mg/kg or diazepam at 3 mg/kg. However, the hypolocomotor activity and impairment of rotarod performance induced by beta-CCM were not antagonized by diazepam at 3 mg/kg. These results indicated that beta-CCM exerts an inhibitory effect on muricide through benzodiazepine receptors and this inhibitory effect was not solely caused by its sedative or motor incordinating activity at the dose ranges used in this study.

Aggression↗
PubMed1990

Evaluation of the neuroprotective action of WEB 1881 FU on hypoglycemia/hypoxia-induced neuronal damage using rat striatal slices.

Effect of WEB 1881 FU on hypoglycemia/hypoxia-induced brain damage in rats was evaluated and compared to findings obtained with idebenone. We used an in vitro model that facilitated the direct monitoring of dopamine release from striatal slices. The response to high K+ stimulation under perfusion of the slices with D-glucose-free Ringer solution (hypoglycemia) decreased at 40 min, and then practically disappeared. WEB 1881 FU at 10(-6) M or idebenone at 10(-6) M significantly protected against impairment of the striatal responses under the conditions of hypoglycemia. Hypoglycemic injury, evidenced by a remarkable neuron loss, necrosis and spongyosis was also ameliorated by these drugs. WEB 1881 FU at 10(-6) M had a protective action against the impairment of striatal responses evoked by NaCN (electron transport inhibitor at site 3) and oligomycin (inhibitor of mitochondrial ATP synthesis), but idebenone at 10(-6) M did not. In light of these observations, the possibility that WEB 1881 FU and idebenone exert neuroprotective actions against hypoglycemic/hypoxic brain injury by activating energy metabolism with different mechanisms from each other has to be considered.

Animals↗
PubMed1990

WEB 1881 FU ameliorates impairment of working memory induced by scopolamine and cerebral ischemia in the three-panel runway task.

Using a repeated acquisition procedure in a 3-panel runway apparatus, the effect of WEB 1881 FU on impairment of working memory produced either by scopolamine or by cerebral ischemia was investigated in rats and compared with those of aniracetam and Ca hopantenate. Intraperitoneal injection of scopolamine at 0.56 mg/kg significantly increased the number of errors (pushes made on the two incorrect panels of the three panel-gates located at each choice point). WEB 1881 FU at 10-32 mg/kg, p.o., caused a dose-related reduction in the increase of errors expected in the scopolamine-treated rats. Aniracetam at 10-100 mg/kg, p.o., or Ca hopantenate at 100 and 560 mg/kg, p.o., also significantly diminished the increase in errors induced by 0.56 mg/kg of scopolamine. Cerebral ischemia for 5 min significantly increased errors in the 3-panel runway task. WEB 1881 FU at 32 and 56 mg/kg, administered p.o. immediately after blood flow recirculation and again 1 hr before the runway test, conducted 24 hr after ischemia, significantly reduced the increase in errors expected to occur after 5 min of ischemia. Aniracetam at 32 and 100 mg/kg, p.o., similarly diminished the increase in errors in ischemic rats. These findings suggest that WEB 1881 FU has a beneficial effect on memory that has been impaired by scopolamine or by cerebral ischemia.

Animals↗
PubMed1989

Endothelin-triggered brain damage under hypoglycemia evidenced by real-time monitoring of dopamine release from rat striatal slices.

The role of endothelin in the pathogenesis of hypoglycemic brain damage in rats was evaluated using an in vitro model with which we could directly monitor the release of dopamine from striatal slices. There was no evidence of impairment in case of non-exposure of the slices to endothelin during 20-40 min of hypoglycemia. The response all but disappeared in striatal slices stimulated with endothelin 10(-5) M twice during 20 min of hypoglycemia. Endothelin-triggered hypoglycemic damage was not observed in the absence of extracellular Ca2+ or in the presence of nifedipine 10(-6) M. Our findings provide strong evidence that endothelin is one etiological factor in the development of hypoglycemic/ischemic brain injury, as a result of interaction with specific receptors which activate the voltage-sensitive Ca2+ channel.

Action Potentials↗
PubMed1989

Neuroanatomical substrates regulating rat conflict behavior evidenced by brain lesioning.

The present study was designed to clarify neural circuits involved in the mediation of behavioral suppression using the Vogel type conflict procedure in rats. Among the brain nuclei inclusive of neuroanatomical substrates of behavioral suppression, lesioning of the central amygdala, mammillary body or frontal cortex led to a significant increase in the punished drinking responses. Lesion of the septum also tended to increase these responses. These results show the key role of these brain areas in mediation of behavioral suppression such as conflict behavior.

Amygdala↗
PubMed1989

Effect of S-adenosyl-L-methionine on impairment of working memory induced in rats by cerebral ischemia and scopolamine.

A repeated acquisition procedure in a 3-panel runway apparatus was used to investigate the effects to S-adenosyl-L-methionine (SAM) on impairment of working memory produced either by cerebral ischemia or by scopolamine in rats. Cerebral ischemia (2-10 min) produced duration-dependent increases in the number of errors (pushes made on the two incorrect panels located at each choice point) and increased latency (time before the rat reached the goal box). The increase in errors induced by a 5 or 10 min period of ischemia decreased gradually in subsequent training sessions, returning to the control levels in 6 days. The increases in both errors and latency induced by 5 min of ischemia were significantly reduced by 100 and 180 mg/kg SAM administered i.p. immediately after blood recirculation and 1 h before a test conducted 24 h after ischemia. SAM at doses up to 180 mg/kg nevertheless failed to reduce the increases in errors and latency if they were induced by 0.56 mg/kg of scopolamine. These results suggest that SAM has a beneficial effect on memory that has been impaired by cerebral ischemia.

Animals↗