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Minoru Narita

Publications and source records attributed to Minoru Narita.

At least 19 recordsLinked to original sources
PubMed2006

Changes in function of NMDA receptor NR2B subunit in spinal cord of rats with neuropathy following chronic ethanol consumption.

Chronic ethanol consumption produces painful neuropathy for which there is no reliably successful therapy, largely due to a lack of understanding of the central mechanisms that underlie the development of the neuropathic pain-like state induced by chronic ethanol treatment. The aim of this study was to investigate what mechanisms contribute to the neuropathic pain-like state induced by chronic ethanol treatment in rats. Mechanical hyperalgesia was clearly observed during ethanol consumption and even after ethanol withdrawal, and lasted for 14 weeks. This hyperalgesia was significantly attenuated by repeated i.p. injection of ifenprodil, a selective NR2B subunit-containing NMDA receptor antagonist. Under these conditions, mRNA and protein levels of NR1, NR2A and NR2B subunits did not change in the spinal cord of chronic ethanol-fed rats. Interestingly, phosphorylated-Ser-1303 NR2B (p-Ser1303-NR2B) subunit was significantly increased in the spinal cord of chronic ethanol-fed rats, whereas p-Tyr1472-NR2B was not affected in the superficial spinal dorsal horn of ethanol-fed rats. These findings suggest that spinal p-Ser1303-NR2B plays a significant role in the development of the ethanol-dependent neuropathic pain-like state in rats.

Alcohol Drinking↗
PubMed2006

Involvement of mGluR5 in the ethanol-induced neuropathic pain-like state in the rat.

Alcohol neuropathy has been thought to involve decreased nerve function following chronic ethanol consumption. However, there is no reliably successful therapy, largely due to a lack of understanding of the central underlying mechanisms. The aim of this study was to investigate the mechanisms that contribute to the neuropathic pain-like state induced by chronic ethanol treatment in rats. Rats were chronically treated with ethanol diet (1.25-5% of ethanol) for over 70 days. Mechanical hyperalgesia was observed during ethanol consumption and even after ethanol withdrawal. Under these conditions, an immunohistochemical study showed an increase in metabotropic glutamate receptor 5 (mGluR5) immunoreactivity in the superficial spinal dorsal horn of chronic ethanol-fed rats. Furthermore, immunoblot analysis revealed that the protein level of mGluR5 was clearly increased following chronic ethanol consumption. These findings support the idea that the increased levels of mGluR5 in the spinal cord may be, at least in part, involved in the induction of ethanol-dependent neuropathic pain-like state.

Alcoholic Neuropathy↗
PubMed2006

Prenatal and neonatal exposure to low-dose of bisphenol-A enhance the morphine-induced hyperlocomotion and rewarding effect.

Bisphenol-A has been extensively evaluated for toxicity in a variety of tests as the most common environmental endocrine disruptors. In the previous study, we reported that prenatal and neonatal exposure to high-dose of bisphenol-A affects the development of central dopaminergic system in the mouse limbic area. The present study was then undertaken to investigate whether prenatal and neonatal exposure to lower dose of bisphenol-A could change the morphine-induced several pharmacological actions such as rewarding effect and hyperlocomotion in mice. Prenatal and neonatal exposure to low-dose of bisphenol-A enhanced the morphine-induced hyperlocomotion and rewarding effect. Additionally, the treatment with bisphenol-A produced an up-regulation of dopamine receptor function to activate G-protein in the mouse limbic forebrain, which is thought to play a critical role for hyperlocomotion and rewarding effects by drugs of abuse. These findings suggest that prenatal and neonatal exposure to low-dose of bisphenol-A can potentiate the central dopamine receptor-dependent neurotransmission, resulting in the supersensitivity of the morphine-induced hyperlocomotion and rewarding effects in the mouse.

Animals↗
PubMed2006

Direct evidence for spinal cord microglia in the development of a neuropathic pain-like state in mice.

The present study was undertaken to further investigate the role of glial cells in the development of the neuropathic pain-like state induced by sciatic nerve ligation in mice. At 7 days after sciatic nerve ligation, the immunoreactivities (IRs) of the specific astrocyte marker glial fibrillary acidic protein (GFAP) and the specific microglial marker OX-42, but not the specific oligodendrocyte marker O4, were increased on the ipsilateral side of the spinal cord dorsal horn in nerve-ligated mice compared with that on the contralateral side. Furthermore, a single intrathecal injection of activated spinal cord microglia, but not astrocytes, caused thermal hyperalgesia in naive mice. Furthermore, 5-bromo-2'-deoxyuridine (BrdU)-positive cells on the ipsilateral dorsal horn of the spinal cord were significantly increased at 7 days after nerve ligation and were highly co-localized with another microglia marker, ionized calcium-binding adaptor molecule 1 (Iba1), but neither with GFAP nor a specific neural nuclei marker, NeuN, in the spinal dorsal horn of nerve-ligated mice. The present data strongly support the idea that spinal cord astrocytes and microglia are activated under the neuropathic pain-like state, and that the proliferated and activated microglia directly contribute to the development of a neuropathic pain-like state in mice.

Animals↗
PubMed2006

Chronic morphine treatment increases the expression of vesicular glutamate transporter 1 in the mouse spinal cord.

Long-term exposure to morphine results in tolerance to morphine-induced antinociception. Here, we found that mice tolerant to morphine exhibited the significant increase in the protein levels of the vesicular glutamate transporter 1 and the synaptic vesicle-specific small G protein Rab3A, but not vesicular glutamate transporter 2 and vesicular gamma-aminobutyric acid transporter. These findings suggest that repeated treatment with morphine enhances excitatory synaptic transmission in the spinal cord, and in turn suppresses the morphine-induced antinociception.

Analgesics, Opioid↗
PubMed2006

Role of gap junction in the expression of morphine-induced antinociception.

The present study was undertaken to investigate whether gap junctional communication could be involved in morphine-induced antinociceptive response using blockers of the gap junctional channel, carbenoxolone and Gap27. Intrathecal pretreatment with either carbenoxolone or Gap27 caused a dose-dependent attenuation of morphine-induced antinociception. Furthermore, the dose-response line for morphine-induced antinociception was shifted to the right by 2.53-fold following intrathecal treatment with carbenoxolone. These findings suggest that gap-junctional-dependent communication in the mouse spinal cord may play, at least in part, a role in the expression of morphine-induced antinociception.

Analgesics, Opioid↗
PubMed2006

Chronic morphine treatment increases the expression of the neural cell adhesion molecule in the dorsal horn of the mouse spinal cord.

It is well known that prolonged exposure to morphine results in tolerance to morphine-induced antinociception. In the present study, we found that mice that were tolerant to morphine-induced antinociception exhibited an increase in immunoreactivity for the neural cell adhesion molecule in the dorsal horn of the spinal cord, which was highly overlapped with immunoreactivity for the increased metabotropic glutamate receptor 5 induced by morphine. These findings support the idea that repeated stimulation of mu-opioid receptors increases the expression of neural cell adhesion molecule and metabotropic glutamate receptor 5. This phenomenon leads to the enhanced excitatory synaptic transmission in the dorsal horn of the spinal cord, and in turn suppresses the morphine-induced antinociception.

Animals↗
PubMed2006

Generalization of NMDA-receptor antagonists to the discriminative stimulus effects of kappa-opioid receptor agonists U-50,488H, but not TRK-820 in rats.

Generalizations of NMDA-receptor antagonists to the discriminative stimulus effects of kappa-opioid receptor agonists in rats were examined. Phencyclidine, MK-801, and ketamine, non-competitive NMDA-receptor antagonists, generalized to the discriminative stimulus effects of U-50,488H, but not those of TRK-820, whereas (+/-)-3-(2-carbaxypiperazine-4-yl) propyl-1-phosphonic acid (CPP), a competitive NMDA-receptor antagonist, and ifenprodil, an NR1/NR2B NMDA-receptor antagonist, did not, suggesting that non-competitive NMDA-receptor antagonists possess U-50,488H-like discriminative stimulus effects in rats. Since U-50,488H and phencyclidine both induce aversive effects, our findings indicate that the cue of the discriminative stimulus effects of U-50,488H and non-competitive NMDA-receptor antagonists may be associated with their aversive effects.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2006

Effects of mu-, delta- and kappa-opioid receptor agonists on methamphetamine-induced self-injurious behavior in mice.

Opioid receptor agonists can differentially modify the behavioral effects of direct/indirect dopamine receptor agonists, such as methamphetamine, cocaine and apomorphine. However, the effects of opioid receptor agonists on high-dose methamphetamine-induced behavior have not yet been clarified. Therefore, the present study was undertaken to investigate the effects of mu (morphine)-, delta (SNC80)- and kappa (U50,488H)-opioid receptor agonists on methamphetamine-induced self-injurious behavior and locomotor activity in mice. Methamphetamine (20 mg/kg) induced severe self-injurious behavior. In a combination test, some opioid receptor agonists significantly attenuated methamphetamine-induced self-injurious behavior, with potencies in the order morphine>buprenorphine (mu-opioid and kappa-opioid receptor agonist/antagonist) >U50,488H, as maximum effects. These results suggest that the stimulation of mu- and kappa-opioid receptors plays an inhibitory role in high-dose methamphetamine-induced stereotypic self-injurious behavior in mice, without affecting locomotor activity.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2006

Role of Src family kinase in the rewarding effect and hyperlocomotion induced by morphine.

The aim of the present study was to investigate the effect of a selective Src family kinase inhibitor, 4-amino-5-(4-chlorophenyl)-(t-butyl)pyrazolo[3,4-D]pyrimidine (PP2), on the rewarding effect and hyperlocomotion induced by morphine. An intracerebroventricular pretreatment with PP2 (0.1-10 nmol/mouse) significantly suppressed the morphine-induced rewarding effect and hyperlocomotion in a dose-dependent manner. We also investigated the changes in immunoreactivities to phosphorylated-Src family kinase in the nucleus accumbens of mice showing the morphine-induced rewarding effect. We found for the first time that Src family kinase is activated in the nucleus accumbens of mice showing the morphine-induced rewarding effect as compared with that found in saline-treated control mice. These findings suggest that Src family kinases in the nucleus accumbens are involved in the rewarding effect and hyperlocomotion induced by morphine.

Animals↗
PubMed2006

Direct evidence of astrocytic modulation in the development of rewarding effects induced by drugs of abuse.

Long-term exposure to pyschostimulants and opioids induced neuronal plasticity. Accumulating evidence suggests that astrocytes actively participate in synaptic plasticity. We show here that a glial modulator propentofylline (PPF) dramatically diminished the activation of astrocytes induced by drugs of abuse, such as methamphetamine (METH) and morphine (MRP). In vivo treatment with PPF also suppressed both METH- and MRP-induced rewarding effects. On the other hand, intra-nucleus accumbens (N.Acc.) administration of astrocyte-conditioned medium (ACM) aggravated the development of rewarding effects induced by METH and MRP via the Janus kinase/signal transducers and activators of transcription (Jak/STAT) pathway, which modulates astrogliosis and/or astrogliogenesis. Furthermore, ACM, but not METH itself, clearly induced the differentiation of multipotent neuronal stem cells into glial fibrillary acidic protein-positive astrocytes, and this effect was reversed by cotreatment with the Jak/STAT inhibitor AG490. Intra-cingulate cortex (CG) administration of ACM also enhanced the rewarding effect induced by METH and MRP. In contrast to ACM, intra-N.Acc. administration of microglia-conditioned medium failed to affect the rewarding effects of METH and MRP in mice. These findings suggest that astrocyte-, but not microglia-, related soluble factors could amplify the development of rewarding effect of METH and MRP in the N.Acc. and CG. The present study provides direct evidence that astrocytes may, at least in part, contribute to the synaptic plasticity induced by drugs of abuse during the development of rewarding effects induced by psychostimulants and opioids.

Analysis of Variance↗
PubMed2006

Direct involvement of orexinergic systems in the activation of the mesolimbic dopamine pathway and related behaviors induced by morphine.

In this study, we investigated the role of orexinergic systems in dopamine-related behaviors induced by the mu-opioid receptor agonist morphine in rodents. Extensive coexpression of tyrosine hydroxylase with orexin receptors was observed in the mouse ventral tegmental area (VTA). The levels of dopamine and its major metabolites in the nucleus accumbens were markedly increased by the microinjection of orexin A and orexin B into the VTA. The subcutaneous morphine-induced place preference and hyperlocomotion observed in wild-type mice were abolished in mice that lacked the prepro-orexin gene. An intra-VTA injection of a selective orexin receptor antagonist SB334867A [1-(2-methylbenzoxazol-6-yl)-3-[1.5]naphthyridin-4-yl urea] significantly suppressed the morphine-induced place preference in rats. Furthermore, the increased level of dialysate dopamine produced by morphine in the mouse brain was significantly decreased by deletion of the prepro-orexin gene. These findings provide new evidence that orexin-containing neurons in the VTA are directly implicated in the rewarding effect and hyperlocomotion induced by morphine through activation of the mesolimbic dopamine pathway in rodents.

Animals↗
PubMed2006

Role of neuronal NR2B subunit-containing NMDA receptor-mediated Ca2+ influx and astrocytic activation in cultured mouse cortical neurons and astrocytes.

The excitatory neurotransmitter glutamate has been shown to mediate such bidirectional communication between neurons and astrocytes. In the present study, we determined the role of N-methyl-D-aspartate (NMDA) receptors on glutamate-evoked Ca(2+) influx into neurons and astrocytes. Either a nonselective NMDA receptor antagonist (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801) or selective NR2B subunit-containing NMDA receptor antagonists ifenprodil and (R,S)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperid inepropanol (Ro25-6981) significantly inhibited the glutamate-evoked Ca(2+) influx into neurons, but not into astrocytes. Furthermore, we investigated whether NR2B subunit-containing NMDA receptor antagonists could suppress the astrocytic activation, as detected by glial fibrillary acidic protein (GFAP; as a specific marker of astrocyte)-like immunoreactivities in mouse cortical astrocytes. Here, we demonstrated that the increases in the level of GFAP-like immunoreactivities induced by glutamate were markedly suppressed by cotreatment with ifenprodil in cortical neuron/glia cocultures, but not in purified astrocytes. These results suggest that NR2B subunit-containing NMDA receptor plays a critical role in not only glutamate-evoked Ca(2+) influx into neurons, but also glutamate-induced astrocytic activation. Thus, glutamate-mediated pathway via NR2B subunit-containing NMDA receptor may, at least in part, contribute to neuron-to-astrocyte signaling.

Aniline Compounds↗
PubMed2006

Chronic pain induces anxiety with concomitant changes in opioidergic function in the amygdala.

Clinically, it has been reported that chronic pain induces depression, anxiety, and reduced quality of life. The endogenous opioid system has been implicated in nociception, anxiety, and stress. The present study was undertaken to investigate whether chronic pain could induce anxiogenic effects and changes in the opioidergic function in the amygdala in mice. We found that either injection of complete Freund's adjuvant (CFA) or neuropathic pain induced by sciatic nerve ligation produced a significant anxiogenic effect at 4 weeks after the injection or surgery. Under these conditions, the selective mu-opioid receptor agonist [D-Ala2,N-MePhe4,Gly5-ol]-enkephalin (DAMGO)- and the selective delta-opioid receptor agonist (+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80)-stimulated [35S]GTPgammaS binding in membranes of the amygdala was significantly suppressed by CFA injection or nerve ligation. CFA injection was associated with a significant increase in the kappa-opioid receptor agonist 2-(3,4-dichlorophenyl)-N-methyl-N-[(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl]acetamide hydrochloride (ICI199,441)-stimulated [35S]GTPgammaS binding in membranes of the amygdala. The intracerebroventricular administration and microinjection of a selective mu-opioid receptor antagonist, a selective delta-opioid receptor antagonist, and the endogenous kappa-opioid receptor ligand dynorphin A caused a significant anxiogenic effect in mice. We also found that thermal hyperalgesia induced by sciatic nerve ligation was reversed at 8 weeks after surgery. In the light-dark test, the time spent in the lit compartment was not changed at 8 weeks after surgery. Collectively, the present data constitute the first evidence that chronic pain has an anxiogenic effect in mice. This phenomenon may be associated with changes in opioidergic function in the amygdala.

Amygdala↗
PubMed2006

Chronic pain-induced emotional dysfunction is associated with astrogliosis due to cortical delta-opioid receptor dysfunction.

It has been widely recognized that chronic pain could cause physiological changes at supraspinal levels. The delta-opioidergic system is involved in antinociception, emotionality, immune response and neuron-glia communication. In this study, we show that mice with chronic pain exhibit anxiety-like behavior and an increase of astrocytes in the cingulate cortex due to the dysfunction of cortical delta-opioid receptor systems. Using neural stem cells cultured from the mouse embryonic forebrain, astrocyte differentiation was clearly observed following long-term exposure to the selective delta-opioid receptor antagonist, naltrindole. We also found that micro-injection of either activated astrocyte or astrocyte-conditioned medium into the cingulate cortex of mice aggravated the expression of anxiety-like behavior. Our results indicate that the chronic pain process promotes astrogliosis in the cingulate cortex through the dysfunction of cortical delta-opioid receptors. This phenomenon may lead to emotional disorders including aggravated anxiety under chronic pain-like state.

Animals↗
PubMed2006

Role of delta-opioid receptor function in neurogenesis and neuroprotection.

The present study was undertaken to evaluate the implication of delta-opioid receptor function in neurogenesis and neuroprotection. We found that the stimulation of delta-opioid receptors by the selective delta-opioid receptor agonist SNC80 [(+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide] (10 nm) promoted neural differentiation from multipotent neural stem cells obtained from embryonic C3H mouse forebrains. In contrast, either a selective micro-opioid receptor agonist, [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO), or a specific kappa-opioid receptor agonist, (-)-trans-(1S,2S)-U-50488 hydrochloride (U50,488H), had no such effect. In addition to neural differentiation, the increase in cleaved caspase 3-like immunoreactivity induced by H2O2 (3 microm) was suppressed by treatment with SNC80 in cortical neuron/glia co-cultures. These effects of SNC80 were abolished by a Trk-dependent tyrosine kinase inhibitor: (8R*,9S*,11S*)-(-)-9-hydroxy-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b,11a-triazadibenzo(a,g)cycloocta(cde)trinden-1-one (K-252a). The SNC80-induced neural differentiation was also inhibited by treatment with the protein kinase C (PKC) inhibitor, phosphatidylinositol 3-kinase (PI3K) inhibitor, mitogen-activated protein kinase kinase (MEK) inhibitor or Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor. These findings raise the possibility that delta-opioid receptors play a crucial role in neurogenesis and neuroprotection, mainly through the activation of Trk-dependent tyrosine kinase, which could be linked to PI3K, PKC, CaMKII and MEK.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2006

[Role of astrocytes in rewarding effects of drugs of abuse].

There are two categories of cells in the central nervous system; neurons and adjacent glial cells including astrocytes, microglia and oligodendrocytes. Accumulating evidence suggests that astrocytes actively participate in synaptic plasticity. On the other hand, long-term exposure to drugs of abuse could induce neuronal plasticity. Astrocytes undergo a process of prolifiration, morphological change, and enhancement of glial fibrillary acidic protein expression, termed activation of astrocytes. Recently, we demonstrated a dramatic increase in reactive astrocytes in the dorsal horn of the spinal cord following repeated in vivo treatment with morphine. We also found that in vivo treatment with morphine, which was associated with the rewarding effect, caused a robust astrocytic activation in the cingulate cortex. These data suggest that astrocytes may contribute to the synaptic plasticity induced by morphine during the development of dependence and tolerance. Therefore, this review focuses on several aspects of astrocytic response and discusses possible roles of astrocytes in the development of dependence and tolerance induced by morphine. We also report here that protein kinase C, Janus kinase/signal transducer and activator of transcription pathway, cyclin-dependent kinase 5 and tyrosine kinase cascade are directly involved in the neuron-glia communication during the development of synaptic plasticity induced by chronic morphine treatment.

Animals↗