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T Nabeshima

Publications and source records attributed to T Nabeshima.

At least 163 records · Page 9Linked to original sources
PubMed1996

Changes in striatal dopamine release in stress-induced conditioned suppression of motility in rats.

Rats received a footshock for 10 min in a chamber with a metallic grid floor, and then placed into the chamber for 30 min after 6 days. The motility of the shocked rats showed a significant decrease (conditioned suppression of motility). In addition, the extracellular dopamine (DA) levels in the striatum were also reduced significantly in in vivo microdialysis study. Thus, dysfunction in the striatal DAergic neuronal systems is responsible for mental stress responses such as conditioned fear stress.

Animals↗
PubMed1996

Effects of the subacute administration of nefiracetam on abnormal behavior in aged rats.

We investigated the effects of nefiracetam on learning and memory by the Morris water maze task and water-finding test, and on emotional behavior by forced swimming, hole-board and open-field tests in old male Kbl Wistar rats aged 90 and 108 weeks. In the water maze task, the acquisition of the task in aged rats was slower than that in young rats. Subacute administration of nefiracetam (1 and 3 mg/kg daily) for 24 days tended to shorten the goal latency to escape onto the platform in a dose-dependent manner in the retention test, conducted 24 days after acquisition training. Nefiracetam (1 mg/kg) administration for 49 days decreased the duration of immobility in aged rats in the forced swimming test. Locomotor activity in young rats during the dark period was significantly higher than that during the light period, while there was no difference in locomotor activity between the light and dark periods in aged rats, suggesting that locomotor activity during the dark period and nocturnal habits may be impaired in aged rats. Subacute administration of nefiracetam for 14 days significantly increased the locomotor activity during the dark, but not light, period in a dose-dependent manner. In addition, nefiracetam given for 38 days, significantly shortened the increased time elapsed before animals started exploring the environment in aged rats compared with young rats in the water-finding tests. These findings suggest that nefiracetam may improve the impaired nocturnal habits and some of emotional behavior in aged rats.

Aging↗
PubMed1996

Reduction in the number of NADPH-diaphorase-positive cells in the cerebral cortex and striatum in aged rats.

Nitric oxide (NO) plays an important role as a diffusible messenger in learning and memory. To determine whether changes in NO production in the brain may be involved in aging-associated brain dysfunction, we measured the performance of aged rats in a radial arm maze task, and carried out histochemical examination of the changes in NADPH diaphorase (NADPH-d)-containing neurons in the brains of aged rats. The performance of aged rats (30 months old) in a radial arm maze task was significantly impaired compared to the performance of young rats (3 months old). The number of neurons containing NADPH-d reactivity in the cerebral cortex and striatum of aged rats was significantly reduced, by approximately 50 and 30 percent, respectively, compared to that in young rats. NO synthase activity in discrete brain regions of aged rats, i.e., in the cerebral cortex, striatum and hippocampus was not different from that in young rats, although the activity in the cerebellum of aged rats was significantly lower than that in young rats. These results suggest that the reduction in the number of NADPH-d-positive cells in the brains of aged rats may be involved in aging-associated learning impairment in rats.

Aging↗
PubMed1996

The effects of single and repeated phencyclidine administration on [125I] iomazenil binding in the rat brain.

We measured [125I] iomazenil binding, labeling the central-type benzodiazepine receptor in 37 discrete rat brain areas following single (7.5 mg/kg, i.p.) and repeated (7.5 mg/kg/day x 14 days, i.p.) treatment with phencyclidine (PCP), a non-competitive antagonist of the N-methyl-D-aspartate(NMDA)-type glutamate receptor, using in vitro quantitative autoradiographic receptor binding assay. Both single and repeated PCP treatment produced heterogeneous changes in the rat brain in a similar manner, the magnitude of change in [125I] iomazenil binding being generally greater in the repeated treatment group than in the single treatment group. A significant increase in [125I] iomazenil binding was observed in the superficial layer (layer I-IV) of the parietal cortex in both of the PCP treatment groups and the CA1 of the hippocampus of the repeated PCP-treated group. There was a significant decrease in [125I] iomazenil binding in the piriform cortex of the repeated PCP-treated group. These results suggest that the blockade of NMDA receptor-mediated glutamatergic neurotransmission by PCP produces the compensational alterations in the central-type benzodiazepine receptor antagonist binding, and that the observed diversity may be due to dissimilar modes of organizations between glutamatergic and the GABA(gamma-aminobutyric acid)-benzodiazepine receptor complex.

Animals↗
PubMed1996

Role of nitric oxide and cyclic GMP in the dizocilpine-induced impairment of spontaneous alternation behavior in mice.

The activation of N-methyl-D-aspartate receptors induces the synthesis of nitric oxide, which activates soluble guanylate cyclase and leads to the formation of cyclic GMP in the brain. The inhibition of nitric oxide production, as well as the blockade of N-methyl-D-aspartate receptors, has been reported to prevent the induction of hippocampal long-term potentiation and learning and memory formation in vivo, although the effects of inhibitors of nitric oxide synthase are still controversial. We investigated the putative role of nitric oxide and cyclic GMP in dizocilpine-induced memory impairment in mice. The nitric oxide synthase inhibitors, NG-nitro-L-arginine methyl ester and 7-nitro indazole, as well as dizocilpine, a non-competitive N-methyl-D-aspartate receptor antagonist, dose-dependently impaired spatial working memory in mice, assessed by their spontaneous alternation behavior in a Y-maze. The inhibitory effects of both NG-nitro-L-arginine methyl ester and dizocilpine on their behavior were completely reversed by 8-bromo-cyclic GMP. Cyclic GMP levels in the cerebellum were reduced by treatment with dizocilpine. NG-Nitro-L-arginine methyl ester and 7-nitro indazole reduced cyclic GMP levels in the cerebral cortex/hippocampus and cerebellum, and the suppressive effect of NG-nitro-L-arginine methyl ester on cyclic GMP levels in the cerebral cortex/hippocampus was reversed by co-treatment with L-arginine. Cyclic AMP levels in the brain were not affected by treatment with either dizocilpine, NG-nitro-L-arginine methyl ester, or 7-nitro indazole. Neither NG-nitro-L-arginine methyl ester nor L-arginine had any effect on monoamine and acetylcholine metabolism in the brain. These results suggest that the reduction in nitric oxide/cyclic GMP production in the brain may be responsible for dizocilpine-induced impairment of spontaneous alternation behavior in a Y-maze.

Animals↗
PubMed1996

Dysfunction of cholinergic and dopaminergic neuronal systems in beta-amyloid protein--infused rats.

Accumulations of beta-amyloid protein are characteristic and diagnostic features of the brain of Alzheimer's disease patients; however, the physiological role of this protein in CNS is unknown. We have previously reported that continuous infusion of beta-amyloid protein into rat cerebral ventricle impairs learning ability and decreases choline acetyltransferase activity, a marker enzyme of cholinergic neuron. In this study, the effects of beta-amyloid protein infusion on the release of neurotransmitters in cholinergic and dopaminergic neuronal systems were investigated by using an in vivo brain microdialysis method. Nicotine-stimulated release of acetylcholine and dopamine in these animals was significantly lower than that in vehicle-infused rats. Further, dopamine release induced by high-K stimulation was decreased in beta-amyloid protein-infused rats compared with vehicle-infused rats. These results suggest that the release of the two transmitters, acetylcholine and dopamine, was decreased by beta-amyloid protein and that learning deficits observed in the beta-amyloid protein-infused rats are partly due to the impairment of neurotransmitter release. Furthermore, continuous infusion of beta-amyloid protein may be a useful method to produce the animal model of Alzheimer's disease.

Acetylcholine↗
PubMed1996

Clinical application of the Biotrack 516 system for determination of theophylline by a turbidimetric latex agglutination inhibition reaction.

Several automated analytical systems for therapeutic drug monitoring (TDM) have been developed. In the present study, theophylline concentration in plasma was measured by the Biotrack 516 system for theophylline, a newly developed automated system based on the turbidimetric latex agglutination inhibition reaction, using whole blood samples obtained from 35 asthmatic patients receiving chronic theophylline therapy. The data were compared with those obtained by high-performance liquid chromatography (HPLC) and fluorescence polarization immunoassay (FPIA). Within-day and between-day precisions for the Biotrack system using blood samples obtained from nine patients ranged from 4.1 to 5.8% and from 2.0 to 6.2%, respectively. Comparison of this system with HPLC and FPIA methods indicated good correlation coefficients of > 0.960, while the respective slope and intercept did not differ from unity and zero. No cross-reactivity of this system with the main metabolites of theophylline and caffeine was observed, thus indicating that the antibodies possess specificity for theophylline. These findings suggest that the Biotrack-516 system is a method that enjoys both accuracy and precision to the same degree as established methods and hence will prove useful in the routine monitoring of plasma theophylline concentrations.

Anti-Asthmatic Agents↗
PubMed1996

Role of nitric oxide in the development of tolerance and sensitization to behavioural effects of phencyclidine in mice.

1. To determine whether nitric oxide (NO) was involved in tolerance and sensitization to the effects of phencyclidine (PCP), we examined NO synthase activity and the number of NADPH-diaphorase (NADPH-d)-positive cells in discrete brain regions of saline-, acute PCP- and repeated PCP-treated mice. We also investigated the effects of a NO synthase inhibitor, NG-nitro-L- arginine methyl ester (L-NAME), on the behavioural changes induced by repeated PCP treatment in mice. 2. Acute PCP (1, 3, and 10 mg kg-1, s.c.) treatment induced dose-dependent hyperlocomotion, motor incoordination and stereotyped behaviours, consisting of sniffing, head movement and ataxia in mice. 3. In mice treated repeatedly with PCP (1, 3, and 10 mg kg-1 day-1), s.c., once a day for 14 days), the sniffing, head movement, ataxia and motor incoordination induced by PCP were attenuated (indicating the development of tolerance to these behaviours), whereas the hyperlocomotion induced by PCP was potentiated (indicating the development of sensitization to hyperlocomotion). The development of tolerance and sensitization to PCP-induced behaviours in the repeated PCP-treated mice was more marked at the dose of 10 mg kg-1 day-1) than at other doses. 4. NO synthase activity in the cerebral cortex and cerebellum, but not in the striatum and hippocampus, was significantly decreased by acute PCP (10 mg kg-1) treatment in comparison with saline treatment, and such changes in activity in the cerebral cortex and cerebellum were reversed by repeated PCP treatment (10 mg kg-1 day-1). 5. The number of neurones containing NADPH-d reactivity in the cerebral cortex, nucleus accumbens, and striatum of acute and repeated PCP-treated mice showed no change in comparison with saline-treated mice. 6. Tolerance to PCP (10 mg kg-1 day-1)-induced ataxia and motor incoordination was significantly attenuated by combined treatment with L-NAME (50 mg kg-1 day-1 i.p.). 7. Sensitization to PCP-induced hyperlocomotion was further enhanced by combined treatment with L-NAME (50 mg kg-1 day-1). However, NG-nitro-D-arginine methyl ester (D-NAME, 50 mg kg-1 day-1, i.p.), a less active enantiomer of L-NAME, had no effect, suggesting a stereospecific mechanism. 8. The PCP-induced behaviours in animals that had exhibited tolerance and sensitization to PCP (10 mg kg-1 day-1) were not influenced by acute L-NAME (5 and 50 mg kg-1, i.p.) or D-NAME (50 mg kg-1, i.p.) treatment. 9. These results suggest that NO may play an important role in the development, but not in the maintenance, of tolerance and sensitization to the effect of PCP in mice.

Animals↗
PubMed1996

Alterations in renal uptake kinetics of the xanthine derivative enprofylline in endotoxaemic mice.

The pharmacokinetics and renal uptake of enprofylline, which is primarily excreted into the urine by an active tubular secretion mechanism, were investigated in endotoxaemic mice by lipopolysaccharide isolated from Klebsiella pneumoniae. Lipopolysaccharide (1 mg kg-1) was infused 2 h before starting the examination, thereby inducing a decrease in the systemic clearance and an increase in the steady-state volume of distribution of enprofylline while inducing no changes in the urinary recovery (> 90%). The protein binding of enprofylline significantly decreased in the presence of lipopolysaccharide. Both the systemic clearance for unbound enprofylline and glomerular filtration rate decreased in the treated mice. A nonlinear relationship was found in both groups between the steady-state unbound plasma concentration and renal uptake of enprofylline after constant infusion for 1 h. The renal uptake rate of enprofylline decreased in the treated mice. Lipopolysaccaharide caused increases in the apparent maximum capacity for renal uptake (Vmax) from 17.3 to 32.2 micrograms h-1 g-1 of kidney and in the Michaelis-Menten constant (Km) from 2.7 to 21.7 micrograms mL-1 and decrease in the nonsaturable uptake rate constant (K4) from 0.87 to 0.43 mL h-1 g-1 of kidney. These results indicate that lipopolysaccharide decreases the renal tubular secretion of enprofylline by inducing a decrease in the renal uptake ability.

Animals↗
PubMed1996

The necessity of adjusting the dosage of zonisamide when coadministered with other anti-epileptic drugs.

Zonisamide (ZNS), a new anti-epileptic drug that exhibits a wide anti-epileptic spectrum, is commonly prescribed concomitantly with other anti-epileptic drugs. The interaction between ZNS and other anti-epileptic drugs was investigated in epileptic patients. The steady state plasma levels of all the anti-epileptic drugs were measured by high-performance liquid chromatography. The concomitant administration of phenobarbital (PB), phenytoin (PHT), or carbamazepine (CBZ) with ZNS significantly decreased the ratio of the steady state plasma concentration to the administered dose (C/D ratio) of ZNS, whereas clonazepam (CZP) and valproic acid (VPA) when administered concomitantly with ZNS did not change the C/D ratio. Significant negative correlations were observed between the C/D ratio of ZNS and the doses of PB, PHT, CBZ, and VPA. On the other hand, the ratio of the plasma concentration of carbamazepine-10,11-epoxide (CBZ-E), the major active metabolite of CBZ, to the plasma concentration of CBZ was significantly decreased by concomitant administration with ZNS, indicating that ZNS inhibits the metabolism of CBZ. These findings show that when ZNS is administered concomitantly with these anti-epileptic drugs, it is necessary to monitor the plasma concentration of ZNS in order to adjust its dosage.

Adolescent↗
PubMed1996

Effects of dietary vegetable oils on behavior and drug responses in mice.

Previously, we noted significant differences in the behavioral patterns of mice fed safflower oil with a very low alpha-linolenate/linoleate ratio and perilla oil with a high alpha-linolenate/linoleate ratio from mothers to offsprings. In this report, we compared the behavior and drug responses in mice fed diets containing six different vegetable oils-corn, rapeseed, soybean, safflower, perilla and a mixture of perilla and safflower oils- for a relatively short period: 8 months after weaning. Soybean oil is a component of most conventional diets and was used as a control. The alpha-linolenate/linoleate ratios of the oils appeared to affect the locomotor activities in a wheel cage: the activity decreased in the order of safflower, the mixture (1:1) and the perilla oil groups. However, the rapeseed oil group exhibited much higher locomotor activity than that expected from the alpha-linolenate/linoleate ratio. Additionally, the rapeseed oil group exhibited unusual behavior patterns, including higher ambulation and rearing activities, faster acquisition of the water maze task and slower habituation behavior as compared with the control group. Susceptibility to pentobarbital anesthesia tended to be higher in the rapeseed oil group. The differences in the alpha-linolenate/linoleate ratios of these oils alone do not account for the observed differences in the behavioral patterns among the six dietary groups. Although we cannot exclude the possibility that the observed behavioral anomaly is due to the unique fatty acid composition of rapeseed oil, we speculate that a factor(s) other than fatty acids in rapeseed oil affected nervous system functions.

Analgesics↗
PubMed1996

The role of nitric oxide in dizocilpine-induced impairment of spontaneous alternation behavior in mice.

We investigated the role played by nitric oxide in the dizocilpine-induced impairment of both spontaneous alternation behavior in a Y-maze and of performance in a multiple-trial passive avoidance task in mice. Dizocilpine (0.1 mg/kg) impaired the spontaneous alternation behavior and the retention of passive avoidance without affecting acquisition in the multiple-trial passive avoidance task. NG-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide (NO) synthase, dose-dependently impaired the spontaneous alternation behavior, but had no effect on either the acquisition or retention of passive avoidance. NG-nitro-D-arginine methylester had no effect on either task. The inhibitory effect of L-NAME on the spontaneous alternation behavior was completely reversed by the coadministration of L-arginine. Pretreatment with L-arginine ameliorated the dizocilpine-induced impairment of spontaneous alternation behavior, but not the impairment of the retention of passive avoidance. S-Nitroso-N-acetylpenicillamine, a generator of NO, completely inhibited the dizocilpine-induced impairment of spontaneous alternation behavior. Finally, the impairment of spontaneous alternation behavior caused by dizocilpine was significantly diminished by pretreatment with dibutyryl cyclic GMP. These results suggest that, although N-methyl-D-aspartate receptors play a critical role in both spatial working memory and long-term memory processes assessed by spontaneous alternation behavior and the passive avoidance, respectively, different neuronal mechanisms may be involved in these two processes. Further, it is suggested that the NO/cyclic GMP system may play a role in spatial working memory.

Animals↗
PubMed1996

[Neuropharmacological effects of sigma receptor ligands: anxiolytic, anti-amnesic and neuroprotective effects].

There is evidence for the existence of two classes of sigma binding sites, termed "site 1" and "site 2", that are distinct from opioid and PCP receptors. Sigma receptor ligands may be useful in the treatment of schizophrenia, since they improve not only positive but also negative symptoms with little extrapyramidal side effects in animal models. In addition, recent experiments have demonstrated that sigma receptor ligands attenuate the motor suppression and colonic motor disturbances seen under mentally stressful situations, stimulate the central cholinergic function thereby ameliorating impairment of learning and memory, and protect cerebral neurons against cerebral ischemic insult. The present review describes the neuropharmacological effects of sigma receptor ligands, especially anxiolytic (anti-stress) effects, ameliorating effects on impairment of learning and memory, and neuroprotective effects.

Animals↗
PubMed1996

[Experimental techniques for developing new drugs acting on dementia (10)--Alzheimer's disease animal model induced by beta-amyloid protein].

To develop an animal model of Alzheimer's disease, beta-amyloid protein was infused into the rat cerebral ventricle for 14 days using a mini-osmotic pump. The performance of some memory tasks in the beta-amyloid protein-treated rats was impaired. Long-term potentiation in the hippocampus was impaired in beta-amyloid-infused rats. The impairment of memory under the infusion could be recovered by two cognitive enhancer drugs. Choline acetyltransferase activity significantly decreased in the frontal cortex and hippocampus but glial fibrillary acidic protein immunoreactivity increased in the cortex both immediately and 2 weeks after cessation of the infusion. Ciliary neurotrophic factor contents in several brain areas in beta-amyloid-infused rat significantly increased. Substance P and microtubule-associated protein, which play an important role in neuronal transmission and construction of neuronal cells, respectively, decreased. Moreover, the release of acetylcholine and dopamine from the cortex/hippocampus and striatum, respectively, in the beta-amyloid-infused rats after depolarization was smaller than that from the control rats. These results suggest that beta-amyloid protein induced dysfunction of the central nervous system in vivo, and that the animal could be used as a model of Alzheimer's disease.

Alzheimer Disease↗
PubMed1996

[Behavioral assessment of neuroleptics (3)--Schizophrenia negative symptoms-like model induced by PCP].

Immobility induced by forced swimming is well known as an animal model of depression. To develop an animal model for the negative symptoms of schizophrenia, in particular, the depressive symptoms, the effect of phencyclidine (PCP) on immobility in the forced swimming test was investigated in mice, since PCP produces negative symptoms-like behavioral changes in humans. Repeated treatment with PCP (10 mg/kg/day, sc, once a day for 14 days) prolonged the immobility time in the forced swimming test 24 hr after the final injection compared with saline treatment; the effect was not obtained by single treatment with PCP (10 mg/kg), or by repeated treatment with methamphetamine (0.3 and 1 mg/kg/day, sc, once a day for 14 days). The enhancing effect of PCP on the immobility persisted for at least 21 days after the withdrawal of the drug. Desipramine (10 mg/kg, po) attenuated the immobility induced by the forced swimming in mice repeatedly treated with saline. The enhancing effect of PCP on the immobility was attenuated by risperidone (0.3 mg/kg), clozapine (3 and 10 mg/kg), and desipramine (20 and 50 mg/kg), whereas haloperidol (0.3 and 1 mg/kg) had no effect. These results suggest that the enhancement of immobility in the forced swimming test brought about by repeated PCP treatment could be used as a model of the negative symptoms, particularly the depression, of schizophrenia.

Animals↗
PubMed1995

Age-related changes in learning and memory and cholinergic neuronal function in senescence accelerated mice (SAM).

The senescence-accelerated mouse (SAM) has been established as a murine model of accelerated aging. We investigated learning ability and memory in various tasks in a SAM strain, SAMP1TA, and in a control strain of SAMR1TA at the ages of 20, 30 and 40 weeks. We also measured choline acetyltransferase (ChAT) and cholinesterase (ChE) activity in the brains of these mice at the same ages. In a Y-maze task, in which short-term memory can be examined, there was no difference in learning ability between SAMP1TA and SAMR1TA at any age. Ability in latent learning and passive-avoidance tasks was less in SAMP1TA at 30 weeks of age than in age-matched SAMR1TA. The level of ChAT activity in the striatum of SAMP1TA was lower, than that of SAMR1TA at the ages of 20 and 30 weeks. At the ages of 40 and 50 weeks, ChE activity in the striatum of SAMP1TA was lower than that of SAMR1TA. These results suggest that SAMP1TA has a deficit, with cholinergic neuronal dysfunction, in learning ability and memory, as shown by impairment of performance in latent learning and long-term memory, but not in short-term memory.

Aging↗