Biomedical subjects

T Nabeshima

Publications and source records attributed to T Nabeshima.

At least 307 records · Page 17Linked to original sources

PubMed1991

Effects of DM-9384, a cyclic derivative of GABA, on amnesia and decreases in GABAA and muscarinic receptors induced by cycloheximide.

The effects of N-(2,6-dimethyl-phenyl)-2-(2-oxo-1-pyrrolidinyl)-acetamide [DM-9384], a cyclic derivative of GABA, were investigated in the cycloheximide (CXM)-induced amnesia animal model using the passive avoidance task. Pre- and post-training and pre-retention test administration of DM-9384 attenuated the CXM-induced amnesia as indicated by prolongation of step-down latency. Aniracetam, another cyclic derivative of GABA, also showed antiamnesic effects. Scopolamine, a muscarinic ACh receptor antagonist, and the GABA antagonists, picrotoxin and bicuculline, all antagonized the antiamnesic effects of DM-9384. CXM decreased the number of GABAA and muscarinic ACh receptor binding sites. DM-9384 not only inhibited this effect but actually increased the latter. These results suggest that DM-9384 attenuates CXM-induced amnesia by interacting with GA-BAergic and AChergic neuronal systems and enhancing protein synthesis in the brain.

Amnesia↗

PubMed1991

Staurosporine facilitates recovery from the basal forebrain-lesion-induced impairment of learning and deficit of cholinergic neuron in rats.

Alzheimer's disease is characterized by the loss of cholinergic neurons in the nucleus basalis of Meynert and by a primary loss of memory function. Since staurosporine has been reported to induce differentiation in human neuroblastoma cells in vitro, we studied the effects of staurosporine on the amnesia induced by basal forebrain-lesion in rats. Staurosporine (0.05 and 0.1 mg/kg intraperitoneal) attenuated the impaired performance of water maze and passive avoidance tasks, even though the drug administration began 2 weeks after the lesion. Moreover, staurosporine (0.1 mg/kg) partially reversed the decrease of choline acetyltransferase activity in the fronto-parietal cortex induced by basal forebrain-lesion. These results suggest that staurosporine attenuates impairment of learning through reversal of damage to cholinergic neurons induced by basal forebrain-lesion. This evidence indicates that neurotrophic factor-like substances may be used in novel therapeutic approaches to Alzheimer's disease.

Alkaloids↗

PubMed1990

Neurotoxicity induced by continuous infusion of quinolinic acid into the lateral ventricle in rats.

Acute intrastriatal injection of quinolinic acid (QA) caused a significant reduction of choline acetyltransferase (ChAT) and glutamic acid decarboxylase (GAD) activities as well as a decrease of the specific binding of [3H]hemicholinium-3. Pretreatment with MK-801 completely blocked the QA-induced neurotoxicity. Continuous infusion of QA into the lateral ventricle resulted in a reduction of hippocampal and cortical ChAT activities while GAD activities were unchanged. These results suggest that continuous infusion of QA into the lateral ventricle could be a useful technique for the study of chronic neurodegenerative diseases including Alzheimer's disease.

Animals↗

PubMed1990

Involvement of AChergic systems in chlordiazepoxide induced impairment of passive avoidance response.

The chlordiazepoxide (CDP)-induced impairment of the passive avoidance response was attenuated by Ro 15-4513, a benzodiazepine inverse agonist, physostigmine and scopolamine at low doses. In a biochemical approach, CDP increased, but Ro 15-4513 decreased the acetylcholine (ACh) levels of cerebral cortex. After the training of passive avoidance, the ACh levels in the hippocampus and cerebral cortex decreased. This change disappeared by pretraining administration of CDP. These results suggest that the effect of CDP on the passive avoidance response was related to AChergic neuronal systems.

Acetylcholine↗

PubMed1990

Attenuation of benzodiazepine-induced passive avoidance deficit by post-training administration of muscimol: interaction with the cholinergic neuronal system.

We examined the involvement of GABAergic neuronal systems in benzodiazepine-induced passive avoidance deficit. Chlordiazepoxide impaired the passive avoidance response dose dependently when it was given prior to training. Post-training administration of muscimol improved the performance of chlordiazepoxide-pretreated mice. The effects of muscimol were antagonized completely by the GABAA antagonist, bicuculline, and the muscarinic acetylcholine receptor antagonist, scopolamine, but not by the benzodiazepine receptor antagonist, flumazenil, when the latter was administered immediately after training. It appears from these results that the GABAergic neuronal system plays an important role in the benzodiazepine-induced passive avoidance deficit by interacting with the cholinergic neuronal system.

Animals↗

PubMed1990

Effects of DM-9384 in a model of amnesia based on animals with GABAergic neuronal dysfunctions.

The effects of N-(2,6-dimethyl-phenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide (DM-9384), a cyclic derivative of GABA, were investigated and compared with those of aniracetam in an animal model of amnesia, using a passive avoidance task with animals that have GABAergic neuronal dysfunctions. Pre- and post-training administration of DM-9384 and aniracetam ameliorated bicuculline-induced amnesia, as indicated by parameters such as % retention and step-down latency. DM-9384 ameliorated picrotoxin-induced amnesia when administered pre-training, but not when administered post-training. Aniracetam failed to improve the picrotoxin-induced amnesia. DM-9384 displaced [3H]muscimol binding to GABAA receptors (-log IC50 = 8.07 M; Hill value = 0.23 +/- 0.04), but failed to displace about 20% of the specific muscimol binding, whereas aniracetam showed only a weak effect (-log IC50 = 3.63 M; Hill value = 0.37 +/- 0.06). From these results, it appears that DM-9384 ameliorated the GABA antagonist-induced amnesia by interacting with some GABAA receptors directly and/or indirectly.

Amnesia↗

PubMed1990

MK-801 ameliorates delayed amnesia, but potentiates acute amnesia induced by CO.

The effects of non-competitive N-methyl-D-aspartate receptor antagonists on amnesia induced by carbon monoxide (CO) were investigated, since they have neuroprotective effects on delayed degeneration induced by ischemia. In the mice exposed to CO, acute and delayed amnesia were induced. (+)-MK-801 and (-)-MK-801 improved the delayed amnesia, but the effects of phencyclidine (PCP) were weak. (+)-MK-801 and PCP potentiated the acute amnesia. From these results, it is suggested that there is a stereoselectivity in the effects of MK-801 on CO-induced amnesia and that CO-induced delayed amnesia animals could be used as an ischemic amnesia model.

Amnesia↗

PubMed1990

Utility of an elevated plus-maze for the evaluation of memory in mice: effects of nootropics, scopolamine and electroconvulsive shock.

An elevated plus-maze consisting of two open and two enclosed arms was employed for an evaluation of memory in mice. Mice in the plus-maze escaped from the open arm to the enclosed arm because mice apparently dislike open and high spaces. The time it took for the mice to move from the open arm to the enclosed arm (transfer latency) was recorded. The transfer latency after the 2nd day was significantly shorter than that on the 1st day when it was recorded at a rate of one trial a day for 5 days. The transfer latency on the 2nd day was significantly prolonged in the mice administered electroconvulsive shock (300 V, 1 s) or scopolamine (20 micrograms, ICV) immediately after the first trial compared to the transfer latency in the control group. The prolongation of transfer latency in the mice administered an electroconvulsive shock was reversed by pretreatment with aniracetam (20 mg/kg, PO), but not tacrine and physostigmine. The prolongation of transfer latency in the mice administered scopolamine was reversed by pretreatment with aniracetam (10 and 20 mg/kg, PO) tacrine (1 and 3 mg/kg, PO), or physostigmine (0.025-0.2 mg/kg, IP). These results suggest that transfer latency may be one of the parameters of learning and memory.

Amnesia↗

PubMed1990

Effects of DM-9384, a pyrrolidone derivative, on alcohol- and chlordiazepoxide-induced amnesia in mice.

The effects of N-(2,6-dimethyl-phenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide (DM-9384), a new pyrrolidone derivative, were investigated on ethanol- and chlordiazepoxide (CDP)-induced amnesia animal model using the passive avoidance task in comparison with aniracetam, another pyrrolidone derivative. Pretraining administration of DM-9384 attenuated ethanol- and CDP-induced amnesia, whereas aniracetam failed to do so. The effects of DM-9384 on CDP-induced amnesia were antagonized by bicuculline, a GABAA receptor antagonist, but not by scopolamine, a muscarinic acetylcholine receptor antagonist and flumazenil, a benzodiazepine receptor antagonist. These results suggest that DM-9384 attenuates CDP-induced amnesia by interacting with the GABAergic neuronal system.

Amnesia↗

PubMed1990

[3H]thienylcyclohexylpiperidine binding activity in brain synaptic membranes treated with Triton X-100.

Binding activity of [3H]thienylcyclohexylpiperidine was examined using rat brain synaptic membranes treated with Triton X-100. This compound is proposed to be a noncompetitive antagonist for the N-methyl-D-aspartate (NMDA)-sensitive subclass of brain excitatory amino acid receptors. The activity decreased in proportion to increasing concentrations of the detergent up to 0.08%. In vitro addition of L-glutamate (Glu) partially restored the decreased activity caused by this Triton treatment, whereas further addition of glycine (Gly) entirely reversed the loss of activity to the level found in membranes extensively washed but not treated with a detergent. These stimulatory effects were found to be due to the acceleration of the association of ligand. The rank order of potentiation of the activity coincided well with that of the affinity for the NMDA-sensitive subclass among numerous Glu analogs. The potentiation by Gly as well as Glu was invariably prevented by competitive NMDA antagonists, such as DL-2-amino-5-phosphonovalerate and (+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate, but not by strychnine. No significant difference was observed between pharmacological profiles of the activities in synaptic membranes treated and not treated with Triton X-100, except haloperidol. The potency of this sigma-ligand to inhibit the activity was greatly reduced by the Triton treatment in the presence of both Glu and Gly. These results suggest that the regulatory properties of Triton-treated synaptic membranes remain unchanged in terms of the interaction within the NMDA receptor complex.

Animals↗

PubMed1990

Behavioral changes induced by stressful situations: effects of enkephalins, dynorphin, and their interactions.

Effects of opioid peptides on behavioral changes induced by stressful situations were investigated. [D-Ala2,Met5]-enkephalinamide and [D-Ala2,D-Leu5]-enkephalin, degrading-enzyme-resistant derivatives of methionine-enkephalin and leucine-enkephalin, respectively, significantly attenuated both environment-induced conditioned suppression of motility and forced swimming-induced immobility in a dose-dependent manner. The [D-Ala2,Met5]-enkephalinamide- and [D-Ala2,D-Leu5]-enkephalin-induced attenuations were antagonized by naloxone at different doses. In contrast, dynorphin A(1-17) and [N-methyl-Tyr1,N-methyl-Arg7,D-Leu8]-dynorphin A(1-8) ethylamide (E 2078), a degrading-enzyme-resistant derivative of dynorphin, significantly potentiated both behavioral changes. The dynorphin- and E 2078-induced potentiations were inhibited by Mr 2266. [D-Ala2,Met5]-enkephalinamide-induced attenuation of environment-induced conditioned suppression of motility and forced swimming-induced immobility was prevented by treatment with dynorphin and E 2078 at the doses that did not affect the behavioral changes. This antagonism by both dynorphin and E 2078 was inhibited by Mr 2266. However, [D-Ala2,D-Leu5]-enkephalin-induced attenuation of both behavioral changes was not affected by either dynorphin or E 2078. These results indicated that activation of the methionine- or leucine-enkephalinergic system attenuates behavioral changes induced by stress, whereas activation of the dynorphinergic system potentiates those changes. Furthermore, the dynorphinergic system may interact with the methionine-enkephalinergic system, but not with the leucine-enkephalinergic system.

Animals↗

PubMed1990

Effects of benzodiazepines on passive avoidance response and latent learning in mice: relationship to benzodiazepine receptors and the cholinergic neuronal system.

The effects of benzodiazepines on learning and memory were investigated, using passive avoidance and latent learning tasks, with particular attention being paid to the possible involvement of benzodiazepine receptors and the cholinergic neuronal system. Benzodiazepines such as diazepam, nitrazepam and chlordiazepoxide (CDP) impaired the passive avoidance response when administered before training, but not when administered immediately after training or before the retention test. CDP also impaired latent learning in the water finding task. State-dependent learning was not observed with CDP at the dose used. A benzodiazepine inverse agonist, Ro 15-4513, and a benzodiazepine antagonist, Ro 15-1788, completely and partially reversed, respectively, the disruptive effects of CDP on learning and memory at the doses which did not enhance learning and memory. The disruptive effects of CDP on learning and memory were partially antagonized by a choline esterase inhibitor, physostigmine, and by a blocker for muscarinic acetylcholine receptors, scopolamine, at the doses which increase acetylcholine release. These results suggest that benzodiazepines induce disruptive effects on learning and memory through benzodiazepine receptors, and that benzodiazepine-induced impairment of learning and memory is, at least in part, the result of the dysfunction of the cholinergic neuronal system.

Animals↗

PubMed1989

Effect of minaprine on cycloheximide-induced amnesia in mice.

The effects of minaprine on cycloheximide-induced amnesia were investigated in a step-down passive avoidance task in mice. Minaprine significantly improved cycloheximide-induced amnesia. This effect was inhibited by scopolamine, but was potentiated by physostigmine. The anti-amnesic effect of minaprine on the cycloheximide-induced memory impairment was also antagonized by a serotonin (5-HT) releaser, p-chloroamphetamine, and by a 5-HT precursor, 5-hydroxytryptophan, whereas a 5-HT1A-selective agonist, 8-hydroxy-2-(di-n-propylamino)tetralin, was inactive. The memory-improving effect of minaprine on cycloheximide-induced amnesia was potentiated by a selective 5-HT2 antagonist, ritanserin. These results suggest that the beneficial effect of minaprine on cycloheximide-induced amnesia may be related not only to cholinergic but also serotonergic neuronal systems (5-HT2 receptors).

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1989

Comparison of the behavioral and biochemical effects of the NMDA receptor antagonists, MK-801 and phencyclidine.

The behavioral and biochemical effects of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 [+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate) were compared with those of phencyclidine (PCP). In the dose range used in this study, MK-801 (0.125-0.5 mg/kg i.p.) produced ataxia and other behavioral responses which were similar to PCP (5-10 mg/kg i.p.). However, turning and backpedalling induced by MK-801 were not dose-dependent and less intense at the dose producing approximately the same level of ataxia as PCP. Neurochemically, MK-801 (0.5 mg/kg i.p.) increased dopamine turnover in the cortex and striatum, but had no effect on 5-HT systems. It was also 3.4 times less potent in inhibiting 5-HT uptake than PCP. These results suggest that the behavioral responses induced by MK-801 involve primarily the PCP receptor and the dopamine system, and that the differences from PCP reflect a reduced effect on the 5-HT neuronal system.

Animals↗

PubMed1989

Effects of metaphit on phencyclidine and serotonin2 receptors.

We have investigated whether metaphit, a derivative of phencyclidine (PCP) which irreversibly binds to a population of PCP receptor sites in rat brain, blocks PCP-induced head-twitch response which is produced through serotonin2 (5-HT2) receptors, and also whether metaphit decreases the capacity of 5-HT2 receptors. Metaphit (1 mumol/rat) had decreased the intensity of PCP-induced head-twitch response and had depleted both PCP and 5-HT2 receptors by 24 h after administration, but it failed to block 5-HT agonist 5-methoxy-N,N-dimethyltryptamine-induced 5-HT1A receptor-dependent behaviors. These results reconfirmed our hypothesis that PCP and 5-HT2 receptors may have very similar binding sites.

Animals↗

PubMed1989

Differential effects of pimozide and SCH 23390 on acquisition of learning in mice.

Our main purpose was to clarify the differences between the effects of dopamine D-1 (SCH 23390) and D-2 (pimozide) antagonists on memory acquisition in a water-finding and a one-trial passive avoidance task with ddY mice. In the water-finding task, pimozide (0.1 and 0.2 mg/kg i.p.) enhanced the acquisition of latent learning of mice although it suppressed exploratory behavior. In contrast, SCH 23390 (0.1 mg/kg i.p.) attenuated the acquisition of latent learning and suppressed exploratory behavior. In the passive avoidance task, pimozide (0.1 and 0.2 mg/kg i.p.) enhanced the acquisition of the passive avoidance response of mice. SCH 23390 (0.05 and 0.1 mg/kg i.p.) failed to enhance the acquisition of the passive avoidance response. These results could suggest that a moderate block of D-2 receptors enhances memory acquisition but blocking D-1 receptors affects it in an opposite way.

Animals↗

PubMed1989

Effects of 5-HT2 receptor antagonist on cycloheximide-induced amnesia in mice.

A role played by serotonergic neuronal system in cycloheximide (CXM)-induced amnesia was studied in mice using a step-down passive avoidance task. CXM (30 mg/kg SC) given immediately after training caused impairment of memory. Nonselective serotonin (5-HT) antagonist methysergide and selective 5-HT2 antagonist ritanserin significantly attenuated impairment of memory caused by CXM. 5-HT1 antagonist (+/-)-pindolol had no effect on CXM-induced amnesia. The antiamnesic effect of ritanserin on CXM-induced amnesia was antagonized by 5-HT (ICV), but not by nonselective 5-HT agonist 5-methoxy-N,N-dimethyltryptamine and 5-HT1A selective agonist 8-hydroxy-2-(di-n-propylamino)tetralin at the dose level which did not cause the memory disruption. Scopolamine antagonized the antiamnesic effects of methysergide and ritanserin on CXM-induced amnesia. These results suggest that 5-HT2 receptors and cholinergic neuronal system may play an important role in memory formation.

Amnesia↗

PubMed1989

The effect of optical isomers of 3,4-methylenedioxymethamphetamine (MDMA) on stereotyped behavior in rats.

The relative potencies of S(+)-, R(-)-3,4-methylenedioxymethamphetamine (MDMA) and S(+)-methylene-dioxyamphetamine (MDA) in inducing stereotyped behavior were determined in comparison with p-chloroamphetamine. S(+)-MDMA was more potent than R(-)-MDMA in eliciting stereotyped behaviors such as sniffing, head-weaving, backpedalling and turning and wet-dog shakes. These results are consistent with the actions of the drug on release of neurotransmitters in which the S(+) enantiomer is more potent. The desmethyl derivative of (+)MDMA, (+)MDA, was more potent than (+)MDMA in eliciting stereotyped behaviors, and produced wet-dog shake behavior.

3,4-Methylenedioxyamphetamine↗