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T Nabeshima

Publications and source records attributed to T Nabeshima.

At least 37 records · Page 2Linked to original sources
PubMed2001

Morphine tolerance and dependence in the nociceptin receptor knockout mice.

Here we report the involvement of nociceptin receptor in tolerance to morphine-induced antinociception and in morphine dependence. There was no different nociceptive perception and antinociceptive effects of morphine between wild-type and the nociceptin receptor knockout mice. Tolerance to morphine (10 mg/kg)-induced antinociception was developed in both wild-type and the nociceptin receptor knockout mice after administration of morphine (10 mg/kg) twice a day for 5 days. When naloxone (5 mg/kg) was administered to mice treated with morphine repeatedly on the 6th day, morphine withdrawal syndrome was observed in both wild-type and the nociceptin receptor knockout mice, which were accompanied by the elevation of cyclic AMP levels. While naloxone benzoylhydrazone (1 mg/kg), a putative antagonist for nociceptin receptor/naloxone benzoylhydrazone-sensitive sites, also induced the morphine withdrawal signs in both wild-type and the nociceptin receptor knockout mice, the jumping signs in the nociceptin receptor knockout mice were less severe than those in wild-type mice. Treatment with naloxone benzoylhydrazone in morphine-dependent wild-type mice caused a significant increase in cyclic AMP levels in the thalamus while it had no effect in the nociceptin receptor knockout mice. The analysis of opioid mu-receptor binding showed no difference between wild-type and the nociceptin receptor knockout mice. These results suggest that the nociceptin receptor/naloxone benzoylhydrazone-sensitive sites contribute to the induction of morphine withdrawal syndrome in part. Furthermore, it is demonstrated that morphine withdrawal syndrome excepting jumping can be induced by naloxone benzoylhydrazone without any changes in the cyclic AMP levels in the thalamus.

Analgesics, Opioid↗
PubMed2001

Spatial memory deficit and neurodegeneration induced by the direct injection of okadaic acid into the hippocampus in rats.

We investigated the effects of okadaic acid (OA), a specific inhibitor of protein phosphatases 1 and 2A, on spatial memory and neuronal survival in rats. Rats were initially trained on a spatial memory task in an eight arm radial maze. Spatial reference and working memory was impaired 1 day after the unilateral microinjection of OA into the dorsal hippocampus. The impairment was transient, and had disappeared by the following day. In contrast, neurodegeneration induced by OA was persistent and extended to the contralateral side 13 days after the injection. These results suggest that OA causes spatial memory impairment and neurodegeneration when injected directly into the hippocampus. Our findings also indicate dissociation between memory impairment and neurodegeneration induced by OA.

Animals↗
PubMed2001

Memory deficits and increased emotionality induced by beta-amyloid (25-35) are correlated with the reduced acetylcholine release and altered phorbol dibutyrate binding in the hippocampus.

In the present study we found that chronic infusion of beta-amyloid fragment (25-35) at nanomolar concentration into rat cerebral ventricle impairs learning and memory. At a concentration of 3 nmol/day but not 0.3 nmol/day, beta-amyloid significantly reduced the spontaneous alternation behavior and the memory performance in the water maze and multiple passive avoidance tests. A significant increase in anxiety was also found in the animals infused with 3 nmol/day beta-amyloid fragment. Memory deficits and the increased emotionality were correlated with a decreased nicotine-evoked acetylcholine release from the frontal cortex/hippocampus, as assessed by microdialysis, in freely moving rats. The amyloid fragment infused either at pico- or nanomolar concentrations reduced the affinity of [3H] phorbol dibutyrate binding, an index of activated protein kinase C (PKC), and increased the total number of binding sites in the hippocampal particulate fraction. Our results suggest that the amnesic and anxiogenic effects of chronic infusion of beta-amyloid (25-35) are related to the decreased acetylcholine release and reduced PKC activation.

Acetylcholine↗
PubMed2001

Difference in toxicity of beta-amyloid peptide with aging in relation to nerve growth factor content in rat brain.

Amyloid beta-peptide (Abeta) is the major constituent of the senile plaques in the brains of patients with Alzheimer's disease. We have demonstrated previously that memory impairment, dysfunction of the cholinergic and dopaminergic neuronal system and morphological degeneration are produced after the continuous infusion of Abeta into the cerebral ventricle in 8-week-old rat. In the present study, we investigated the toxicity of Abeta in infant (10 days old), adult (8 weeks old) and aged (20 months old) rats in relation to nerve growth factor (NGF) content in various regions of the brain. After a 2-week-infusion, choline acetyltransferase (ChAT) activity was significantly decreased in the hippocampus of adult, but not infant or aged rats. NGF levels in the hippocampus were increased only in adult rats. These results suggest that Abeta is toxic only in the matured adult brain, and that the mechanism of toxicity is related to NGF synthesis.

Aging↗
PubMed2001

The Effects of Aging on the Multifocal Electroretinogram.

Purpose: In order to use multifocal electroretinogram (m-ERG) for clinical assessment, we investigated the effects of aging on waves of the first and second order kernels of the m-ERG.Subjects and Methods: m-ERGs were recorded from 93 eyes (refractive error 0 to -3. 0 D) of 56 normal subjects (range, 12-79, mean, 44.2 +/- 20. 7 years of age) using the Visual Evoked Response Imaging System (VERIS Science((R)), version 3.0.1). We analyzed effects of aging on the response densities and the peak latencies of the first positive wave (P 1) of the first order kernel and the second and third positive waves (P 2 and P 3) of the second order kernel.Results: The response densities of the P 1 and P 2 waves significantly decreased, and the peak latencies of the P 1, P 2 and P 3 were significantly prolonged (P < 0.05) in the subjects above 50 years old.Conclusion: The results suggested that the aging effect on the m-ERG should be considered when evaluating retinal function using m-ERGs in basic and clinical studies.

Journal Article↗
PubMed2001

Phencyclidine impairs latent learning in mice: interaction between glutamatergic systems and sigma(1) receptors.

The effect of phencyclidine (PCP) on latent learning was investigated using a one-trial water-finding task in mice. Mice without water deprivation were given PCP or saline before a training trial, which consisted of exposure to a novel open-field environment with an alcove containing a water tube. Twenty to twenty-four hours after water deprivation, animals were placed in the same apparatus and the time required to find the water tube measured (test trial). Saline-treated trained mice showed a significantly shorter time to find the water tube during the test trial (finding latency) than naive mice that had not been trained. When PCP (1mg/kg i.p.) was administered before the training trial, the finding latency was significantly prolonged in comparison with that in the saline-treated mice, indicating that PCP induced impairment of latent learning. 1-(3,4-Dimethoxy-phenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride (SA4503: 0.3 mg/kg s.c.) and (+)-pentazocine (1 mg/kg s.c.), selective sigma(1) receptor agonists, or D-cycloserine (10 and 30mg/kg, s.c.), a glycine binding site agonist, significantly counteracted the PCP-induced impairment of latent learning, whereas (+)-SKF-10,047 (0.1-3 mg/kg s.c.), a putative sigma(1) receptor agonist, did not. The ameliorating effects of SA4503 and (+)-pentazocine were antagonized by N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy) phenyl) ethylamine (NE-100: 1 mg/kg i.p.), a selective sigma(1) receptor antagonist. SA4503 also ameliorated the impairment of latent learning induced by dizocilpine, a non-competitive N-methyl-D-aspartate receptor antagonist, the effect being antagonized by NE-100. These results suggest that PCP induces an impairment of latent learning, this effect being mediated via glutamatergic systems, and that activation of sigma(1) receptors ameliorates impairment of latent learning induced by PCP.

Animals↗
PubMed2001

Involvement of cyclic AMP systems in morphine physical dependence in mice: prevention of development of morphine dependence by rolipram, a phosphodiesterase 4 inhibitor.

In this study, we examined whether morphine dependence was inhibited by rolipram, a cyclic AMP selective phosphodiesterase inhibitor in mice, since a role for the cyclic AMP systems in the development of morphine dependence has been reported. Mice, which received morphine (10 mg kg(-1) s.c.) twice a day for 5 days showed withdrawal syndromes such as jumping, rearing and forepaw tremor following naloxone challenge (5 mg kg(-1) i.p.) on the 6th day. Such mice exhibited a significant elevation of cyclic AMP levels in the thalamus compared to control mice. However, co-administration of rolipram (1 mg kg(-1) i.p.) with morphine for 5 days significantly attenuated the severity of the withdrawal syndrome and the increase in the cyclic AMP levels after the administration of naloxone. In naïve mice, acute morphine treatment (10 mg kg(-1) s.c.) decreased cyclic AMP levels in the thalamus and cerebral cortex 10 min later. The decrease of cyclic AMP levels induced by acute morphine treatment was blocked by co-administration of rolipram (1 mg kg(-1) i.p.). However, acute rolipram did not affect the naloxone-precipitated morphine withdrawal syndrome. These results suggest that the elevation of the cyclic AMP levels is involved in the development of morphine withdrawal syndrome and that blockade of the morphine-induced reduction of cyclic AMP levels by chronic rolipram inhibits the development of dependence and the behavioural and biochemical changes induced by naloxone. Furthermore, rolipram may be a useful drug for attenuating the development of morphine dependence.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

Enhancement of hippocampal LTP, reference memory and sensorimotor gating in mutant mice lacking a telencephalon-specific cell adhesion molecule.

Telencephalin (TLCN) is a cell adhesion molecule selectively expressed in the telencephalon of the mammalian brain. The mutant mice lacking TLCN had no detectable abnormalities in their neural development and synaptic structures. Ablation of TLCN increased the hippocampal long-term potentiation and its saturation level. The TLCN mutation selectively enhanced the performance of the radial maze and water-finding tasks, learning tasks with appetitive reinforcers, but not the contextual fear conditioning and Morris water maze tasks with aversive stimuli for conditioning. Furthermore, the TLCN mutant mice showed an increase of prepulse inhibition of the acoustic startle response. These results suggest that TLCN is a determinant of the dynamic range of synaptic plasticity and plays roles in reward-motivated learning and memory and sensorimotor gating.

Animals↗
PubMed2001

[The mechanisms of morphine dependence and it's withdrawal syndrome: study in mutant mice].

To investigate the involvement of catecholamines and/or the cyclic AMP (cAMP) systems in the development of drug dependence, we examined whether morphine dependence was developed in tyrosine hydroxylase (TH) heterozygous (TH+/-) and cAMP response element binding protein (CREB) binding protein (CBP) heterozygous (CBP+/-) mice. Morphine (10 mg/kg) induced place preference in the wild-type mice. In the TH+/- and CBP+/- mice, however, we could not find any morphine-induced place preference. When the wild-type mice pretreated with morphine (10 mg/kg) twice a day for 5 days were challenged with naloxone (5 mg/kg), they showed increased numbers of jumping, rearing and forepaw tremor as a sign of withdrawal symptom and increased level of cAMP in the thalamus/hypothalamus, but not in the striatum. However, increased numbers of jumping and forepaw tremor in the TH+/- and CBP+/- mice and increased level of cAMP in the thalamus/hypothalamus of TH+/- mice were not observed. These results suggest that catecholamines and CBP are involved in the development of morphine dependence, and that some changes in the catecholaminergic and/or cAMP system induced by repeated morphine treatment play an important role in the addiction of morphine.

Animals↗
PubMed2001

[Effects of stimulus intensity on multifocal electroretinograms].

PURPOSE: To investigate origins of responses of the second order kernel components of multifocal electroretinograms (m-ERGs), the influence of stimulus intensities on the waveform were studied. SUBJECTS AND METHODS: M-ERGs were recorded from 20 normal eyes of 14 normal adults using a Visual Evoked Response Imaging System with 19 hexagonal stimulus elements with light intensities of 6.3, 20, 63, 200, or 331 cd/m2. The response densities and implicit times of the first (N1, P1, N2) and the second order kernel components (P1, N1, P2, N2, P3, N3) of the m-ERGs were measured. RESULTS: The components were divided into two groups based on the behavior of the each component to the stimulus intensity change. The first group consisted of all the first order kernel components and P1 and N1 of the second order kernel components whose response densities were significantly larger (p < 0.05) than those of components elicited by stimulus of one grade lower intensity. The second group consisted of N2, P3, and N3 of the second order kernel components whose response densities did not increase when the stimulus intensity was increased from 200 to 331 cd/m2. CONCLUSION: It is probable that in the second order kernel components, the origin of P1, N1, and P2 is different from N2, P3, and N3 because the response to stimulus intensity of the two groups of components was different.

Adult↗
PubMed2001

Molecular mechanism of cholinergic dysfunction and cognitive deficits induced by amyloid beta-peptide.

Amyloid beta-peptide (A beta) plays a critical role in the development of Alzheimer's disease (AD). Much progress has been made in understanding this age-related neurodegenerative disorder; thus an insight into the cellular actions of A beta and resulting functional consequences may contribute to preventive and therapeutic approaches for AD. In this review, recent evidence of A beta-induced brain dysfunction, especially cholinergic impairment and memory deficits, is summarized. Moreover, proposed mechanisms for A beta-induced neurotoxicity such as oxidative stress, ion-channel formation, and A beta-receptor interaction are discussed.

Amyloid beta-Peptides↗
PubMed2001

[Neuroactive steroid and stress response].

Dehydroepiandrosterone sulfate (DHEAS), a neuroactive steroid, has been demonstrated to bind to sigma 1 receptors, and it has antidepressive effects in the forced swimming test. We used the conditioned fear stress, which is useful for investigating the pathogenesis of mood disorders. DHEAS attenuated the conditioned fear stress response in mice, the effects being antagonized by a sigma 1 receptor antagonist. It is interesting that, the DHEAS contents and number of apoptotic cells in the brain of mice showing conditioned fear stress response were decreased and increased, respectively, compared with those in the nonstressed mice. DHEAS prevented the expression of apoptosis induced by conditioned fear stress. These findings suggest that the imbalance of neuroactive steroids and the expression of apoptosis play an important role in the expression of conditioned fear stress response and that the use of DHEAS is a novel therapeutic approach for at least some mood disorders.

Animals↗
PubMed2000

Involvement of nitric oxide in phencyclidine-induced place aversion and preference in mice.

The present study investigated the involvement of nitric oxide (NO) in phencyclidine (PCP)-induced place aversion and preference in the place conditioning paradigm. PCP-induced place aversion in naive mice was dose-dependently attenuated by administration of N(G)-nitro-L-arginine methyl ester (L-NAME), a NO synthase (NOS) inhibitor, during the conditioning. The NOS activity and dopamine (DA) turnover in the hippocampus in mice showing PCP-induced place aversion were decreased, such changes being restored by administration of L-NAME during the conditioning. On the other hand, PCP-induced place preference in mice pretreated with PCP for 28 days was not attenuated by administration of L-NAME during the conditioning. Although NOS activity was not changed, the DA turnover in the cerebral cortex was increased in mice showing PCP-induced place preference. In mice pretreated with L-NAME and PCP for 28 days before the place conditioning paradigm, PCP neither induced place preference, nor changed the NOS activity or DA turnover. These results suggest that NO is involved in the acquisition of PCP-induced aversive effects, and in the development of PCP-induced preferred effects. Further, the functional change of the DAergic neuronal system mediated by NO in the hippocampus and cerebral cortex may be necessary for the expression of aversive effects and development of preferred effects, respectively, induced by PCP.

Animals↗
PubMed2000

Neurobehavioral alterations in mice with a targeted deletion of the tumor necrosis factor-alpha gene: implications for emotional behavior.

Tumor necrosis factor-alpha (TNF-alpha) is emerging as an important modulator of the function of the central nervous system. In the present study, we investigated a role of endogenous TNF-alpha in cognitive and emotional function using mice with targeted deletions of the TNF-alpha gene. TNF-alpha-(-/-) mice showed normal diurnal rhythms of spontaneous locomotor activity and cognitive functions. Emotional behavior in the mutant mice, however, was significantly altered, which manifested in the performance in the open-field, elevated plus maze, and forced swimming tests. The altered performance in the elevated plus maze test was significantly alleviated by treatment with diazepam. Postmortem brain analysis of TNF-alpha-(-/-) mice revealed a significant increase in serotonin metabolism in the brain. These findings suggest a role for endogenous TNF-alpha in emotional behavior, which may possibly be related to alterations of serotonine metabolism.

Animals↗
PubMed2000

Spatiotemporal expression of BDNF in the hippocampus induced by the continuous intracerebroventricular infusion of beta-amyloid in rats.

The beta-amyloid protein (Abeta) is the major component of senile plaques found in the brain in Alzheimer's disease (AD). Its neurotoxic properties in vivo, however, are not well defined. Since the expression of neurotrophin genes is considered an important component of the intrinsic neuroprotective response to insults, we analyzed the gene expression of neurotrophins in the brains of rats which received a continuous infusion of Abeta-(1-42) into the cerebroventricle. Northern blot analysis revealed a significant increase in brain-derived neurotrophic factor (BDNF) expression in the hippocampus but no change in the cerebral cortices. The alteration peaked on days 3-7 and returned to the basal level on day 14 after the start of Abeta-(1-42) infusion. No significant changes in nerve growth factor or neurotrophin-3 mRNA expression were observed. The infusion of Abeta-(1-40) and (25-35) also triggered the expression of BDNF mRNA, whereas neither Abeta-(40-1) nor (1-16) had any effect. In situ hybridization histochemistry revealed that the expression mainly occurred in the hilus and granular layer of the dentate gyrus and to a lesser extent in the pyramidal neurons of the CA1 region. These results demonstrate that the continuous intracerebroventricular infusion of Abeta induces selective and spatiotemporal expression of BDNF mRNA in the hippocampus.

Alzheimer Disease↗
PubMed2000

Involvement of brain-derived neurotrophic factor in spatial memory formation and maintenance in a radial arm maze test in rats.

Brain-derived neurotrophic factor (BDNF) regulates both short-term synaptic functions and activity-dependent synaptic plasticity such as long-term potentiation. In the present study, we investigated the role of BDNF in the spatial reference and working memory in a radial arm maze test. The radial arm maze training resulted in a significant increase in the BDNF mRNA expression in the hippocampus, although the expression in the frontal cortex did not change. When spatial learning was inhibited by treatment with 7-nitroindazole, an inhibitor of brain nitric oxide synthase, the increase in the hippocampal BDNF mRNA did not occur. To clarify the causal relation between BDNF mRNA expression and spatial memory formation, we examined the effects of antisense BDNF treatment on spatial learning and memory. A continuous intracerebroventricular infusion of antisense BDNF oligonucleotide resulted in an impairment of spatial learning, although the sense oligonucleotide had no effect. Treatment with antisense, but not sense, BDNF oligonucleotide was associated with a significant reduction of BDNF mRNA and protein levels in the hippocampus. Furthermore, treatment with antisense BDNF oligonucleotide in rats, which had previously acquired spatial memory by an extensive training, impaired both reference and working memory. There were no differences in locomotor activity, food consumption, and body weight between the antisense and sense oligonucleotide-treated rats. These results suggest that BDNF plays an important role not only in the formation, but also in the retention and/or recall, of spatial memory.

Analysis of Variance↗