Biomedical subjects

M Misawa

Publications and source records attributed to M Misawa.

At least 73 records · Page 4Linked to original sources

PubMed1997

Antisense oligodeoxynucleotide to delta opioid receptors blocks cocaine-induced place preference in mice.

The effect of intracerebroventricular (i.c.v.) treatment with antisense oligodeoxynucleotide (A-oligo) to delta opioid receptor mRNA on cocaine-induced place preference was examined in mice. Cocaine (10 mg/kg, s.c.) produced a significant place preference. I.c.v. treatment with A-oligo (0.001-1 microg/mouse) dose-dependently attenuated the cocaine (10 mg/kg, s.c.)-induced place preference, although mismatched oligodeoxynucleotide (1 microg/mouse, i.c.v.) was ineffective. In the present study, we found that the selective reduction in number and/or function of central delta opioid receptors by A-oligo suppresses the cocaine-induced place preference. These results suggest that the conditioned reward by cocaine may be partially mediated by central delta opioid receptors.

Animals↗

PubMed1997

Aggravation of DMCM-induced seizure by nitric oxide synthase inhibitors in mice.

The present study investigated the effects of nitric oxide synthase (NOS) inhibitors on the seizure threshold of DMCM in mice. The seizure threshold of DMCM was evaluated using an intravenous infusion technique. The threshold of DMCM was significantly decreased by pretreatment with N-nitro-L-arginine (NOARG; 8 mg/kg) and N-nitro-L-arginine methyl ester (L-NAME; 100 mg/kg), but not with D-NAME. Furthermore, these NOS inhibitors also decreased the threshold for pentylenetetrazole-induced seizure. However, the threshold for caffeine-induced seizure was not affected by NOARG. These results suggest that the endogenous NO system may play an important role in the expression of seizure by GABA(A) receptor inhibitory agents (DMCM and PTZ).

Animals↗

PubMed1997

Antisense oligodeoxynucleotide to delta opioid receptors attenuates morphine dependence in mice.

The effect of intracerebroventricular (i.c.v.) treatment with antisense oligodeoxynucleotide (A-oligo) to delta opioid receptor mRNA on the morphine-induced place preference and naloxone-precipitated jumping was examined in morphine-dependent mice. Morphine (5 mg/kg, s.c.) produced a significant place preference. I.c.v. pretreatment with A-oligo (0.01-1 microg/mouse) dose-dependently attenuated this morphine (5 mg/kg, s.c.)-induced place preference, while mismatched oligodeoxynucleotide (M-oligo; 1 microg/mouse, i.c.v.) was ineffective. Naloxone (3 mg/kg, s.c.) precipitated jumping in morphine-dependent mice. I.c.v. pretreatment with A-oligo (1 microg/mouse) attenuated this naloxone (3 mg/kg, s.c.)-precipitated jumping in morphine-dependent mice, while M-oligo (1 microg/mouse, i.c.v.) was ineffective. These data demonstrate that the selective reduction in supraspinal delta opioid receptor function caused by pretreatment with A-oligo attenuated the morphine-induced place preference and naloxone-precipitated jumping in morphine-dependent mice, suggesting that the rewarding effect of and physical dependence on morphine may be modulated by central delta opioid receptors.

Animals↗

PubMed1997

Attenuation of mecamylamine-precipitated nicotine-withdrawal aversion by the 5-HT3 receptor antagonist ondansetron.

The effect of ondansetron (0.01-0.1 mg/kg, s.c.), a selective 5-HT3 receptor antagonist, on mecamylamine-precipitated nicotine-withdrawal aversion was examined in the conditioned place preference paradigm. Male Sprague-Dawley rats were chronically treated subcutaneously with 9 mg/kg/day (-)-nicotine tartrate using an osmotic minipump. After nicotine treatment for 7 days, mecamylamine (1 mg/kg, s.c.), a nicotinic receptor antagonist, produced place aversion in nicotine-dependent rats. This aversive effect was dose-dependently antagonized by pretreatment with ondansetron 30 min prior to the conditioning. These results suggest that ondansetron may attenuate the place aversion associated with nicotine withdrawal, and may be useful for the treatment of nicotine dependence.

Animals↗

PubMed1997

Neural reflex-mediated tracheal response during bronchoconstriction induced by ovalbumin antigen in guinea pigs.

1. The biphasic reflex tracheal response (constriction followed by dilatation) occurred during bronchoconstriction induced by inhalation of ovalbumin antigen (OA) in sensitized guinea pigs. 2. The reflex tracheal constriction was largely reduced by atropine, and the dilatation was inhibited by propranolol and N omega-nitro-L-arginine methyl ester (L-NAME). The noradrenaline, adrenaline, cyclic AMP, and cyclic GMP contents in the tracheal segment were significantly higher during reflex tracheal dilatation. 3. These findings suggest that cholinergic nerves may mediate reflex tracheal constriction and that adrenergic and NOergic nerves may mediate the ensuing reflex tracheal dilatation.

Allergens↗

PubMed1997

Generalization of D-, L- and DL-chlorpheniramine and zolantidine to the discriminative stimulus effects of cocaine and methamphetamine.

We recently demonstrated that some H-antagonists have cocaine or methamphetamine-like discriminative stimulus effects. In the present study, the effects of optical isomers of chlorpheniramine (D-, L- and DL-forms) on the discriminative stimulus effects of cocaine and methamphetamine were examined in rats trained to discriminate between cocaine (10.0 mg/kg) or methamphetamine (1.0 mg/kg) and saline, to determine whether these effects of H1-antagonists are mediated by the blockade of H-receptors. In generalization tests with optical isomers of chlorpheniramine, the D-, L- and DL-forms all completely generalized to the discriminative stimulus effects of cocaine, but did not generalize to those of methamphetamine. Dose-generalization by the optical isomers of chlorpheniramine to the discriminative stimulus effects of cocaine did not correlate with the H-antagonistic potency of these drugs. These results suggest that all of the optical isomers of chlorpheniramine have cocaine-like discriminative stimulus effects, but that these effects are not mediated by H1-receptor blockade. On the other hand, the H2-antagonist, zolantidine, generalized to the discriminative stimulus effects of methamphetamine, but not to those of cocaine, suggesting that zolantidine may have methamphetamine-like discriminative stimulus effects. In the present study, GBR12909 (dopamine uptake inhibitor) completely generalized to the discriminative stimulus effects of cocaine, but not to those of methamphetamine, whereas apomorphine (dopamine receptor agonist) generalized more potently to the discriminative stimulus effects of methamphetamine than to those of cocaine. These findings imply that although the dopaminergic system plays an important role in the discriminative stimulus effects of both cocaine and methamphetamine, there may be differences between their effects.

Animals↗

PubMed1997

[Opioid receptor types and dependence].

The existence of mu, delta and kappa opioid receptors in the central nervous system is well documented. The present review focuses on the relationships between opioid receptor types and physical and psychic dependences. Mu and delta, but not kappa opioid receptor agonists produce physical dependence. From behavioral, biochemical and molecular biological studies, it is suggested so far that development of physical dependence on morphine results predominantly from an activation of mu 1 and mu 2 opioid receptors which causes functional changes in Gi/o, adenylate cyclase, protein kinases A and C, beta-adrenoceptor and NMDA receptor in the locus coeruleus. Recently, there have been significant advances in studies on psychic dependence. Mu and delta opioid receptor agonists produce psychic dependence, but kappa opioid receptor agonists rather produce an aversive effect. Activation of the mesolimbic dopamine system may lead to psychic dependence on opioids. Mu and delta 1 opioid receptor agonists activate the mesolimbic dopamine system to induce a rewarding effect, whereas the rewarding effect of delta 2 opioid receptor agonists may be produced through a non-dopaminergic system. There are complicated interactions among opioid receptor types. The activation of kappa opioid receptor suppresses physical and psychic dependences on mu and delta opioid receptor agonists, but the activation of delta opioid receptor potentiates the dependence on mu opioid receptor agonists. The clinical use of morphine in patients with cancer pain won't develop dependence probably due to the balance of the opioid system coming from these interactions.

Animals↗

PubMed1997

Abnormal modulation of cholinergic neurotransmission by endogenous nitric oxide in the bronchus of rats with hyperresponsiveness induced by allergen challenge.

The involvement of endogenous nitric oxide (NO) in bronchial cholinergic neurotransmission was compared between normal rats and airway hyperresponsive (AHR) rats. Male Wistar rats were sensitized and repeatedly challenged with dinitrophenylated (DNP)-Ascaris antigen. Twenty-four hours after the last antigenic challenge, enhancements of both the electrical field stimulation (EFS)-induced bronchoconstriction and acetylcholine (ACh) release were observed. NG-Monomethyl-L-arginine (L-NMMA; NO synthase inhibitor, 0.1 mM) augmented the EFS-induced bronchoconstriction and ACh release without affecting exogenously applied ACh-induced bronchoconstriction in normal rats. Interestingly, the augmentative effects of L-NMMA seen in normal rats were not manifested in AHR rats. Sodium nitroprusside inhibited the EFS-induced bronchoconstriction in a concentration-dependent manner; the inhibition was much larger than that of exogenously applied ACh-induced constriction in both normal and AHR rats. Furthermore, dibutyryl cGMP (3 mM) inhibited the EFS-induced bronchoconstriction with no effect on the ACh-induced bronchoconstriction in both normal and AHR rats. These findings suggest that endogenous NO may have a modulatory role in bronchial cholinergic neurotransmission in normal rats and that the augmented ACh release in the AHR rats may result from the defect of endogenous NO-induced modulation of cholinergic nerve transmission.

Acetylcholine↗

PubMed1996

Mecamylamine-precipitated nicotine-withdrawal aversion in rats.

The present study examined a rapid and convenient model for evaluating nicotine dependence using the conditioned place preference paradigm. Rats were chronically infused subcutaneously with 9 mg/kg per day nicotine using an osmotic minipump. After nicotine infusion for 7 days, the nicotinic receptor antagonist mecamylamine produced a place aversion in nicotine-dependent rats, but not in acute nicotine-treated rats or sham-operated rats. These results suggest that the mecamylamine-precipitated withdrawal aversion in rats chronically treated with nicotine may result from physical dependence on nicotine, and may be useful for studying the physical dependence on nicotine.

Analysis of Variance↗

PubMed1996

Involvement of the opioid system in the anxiolytic effect of diazepam in mice.

In the present study, the anticonflict effect of diazepam was significantly abolished by pretreatment with naloxone, beta-funaltrexamine or nor-binaltorphimine but not naltrindole, using a Vogel-type conflict paradigm in mice. However, naloxone alone had a significant proconflict effect, and beta-funaltrexamine alone tended to produce a proconflict effect. Spontaneous drinking behavior was not affected by treatment with diazepam and nor-binaltorphimine. In addition, nor-binaltorphimine had no effect on diazepam-induced motor incoordination, hypothermia or anticonvulsant action, respectively. Moreover, the stable dynorphin analog E2078 ([N-methyl-Tyr1, N-alpha-methyl-Arg7-D-Leu8]dynorphin A-(1-8) ethylamide) and the highly selective kappa-opioid receptor agonist U50,488H (trans-3,4-dichloro-N-(2-(1-pyrrolidinyl)cyclohexyl)benzenacetamide++ + methanesulfonate hydrochloride) produced a significant anticonflict effect, which was completely antagonized by pretreatment with nor-binaltorphimine. These findings suggested that the kappa-opioid system may play an important role in the anxiolytic effect of benzodiazepine and the regulation of anxiety.

Analgesics, Non-Narcotic↗

PubMed1996

Characteristics of vagal reflex-mediated tracheal response induced by bronchoconstriction in guinea pigs.

The reflex tracheal response induced by bronchoconstriction was investigated using a newly devised tracheo-bronchi preparation in anesthetized guinea pigs. Tracheal constriction and subsequent dilatation were observed in response to bronchoconstriction induced by the inhalation of 0.001-0.01% histamine and 0.003-0.03% acetylcholine. These tracheal responses were abolished by cervical vagotomy or treatment of the tracheal site with 1% tetrodotoxin. Tracheal constriction and dilatation were significantly inhibited by 0.1% atropine and 1% propranolol, respectively. When high tracheal tone was induced by 0.01% serotonin, the residual tracheal dilatation observed in the presence of propranolol was enhanced, while dilatation was completely inhibited by 1% hexamethonium. Dilatation was also suppressed by 1% N omega-nitro-L-arginine methyl ester (L-NAME) and 1% methylene blue. The tracheal constriction produced by bronchoconstriction was significantly enhanced by propranolol 2 mg/kg, i.v. and L-NAME 10 mg/kg, i.v. These results demonstrate that a vagally mediated reflex tracheal response (constriction followed by dilatation) is induced by bronchoconstriction in anesthetized guinea pigs. Cholinergic nerves may mediate the constriction, and adrenergic and nonadrenergic noncholinergic (NANC) inhibitory nerves may mediate the dilatation. Furthermore, NO may be involved in the NANC reflex tracheal dilatation.

Acetylcholine↗

PubMed1996

In vitro differentiation of murine Sca-1+Lin- cells into myeloid, B cell and T cell lineages.

Hematopoietic progenitor cells were shown to be capable of differentiating into myeloid, B cell and T cell lineages. We used a two-step culture system in which enriched murine hematopoietic progenitors in bone marrow were first plated in viscid culture medium containing methylcellulose, erythropoietin (EPO), stem cell factor (SCF) and interleukin (IL)-7. One thousand enriched murine marrow cells formed 53.5 +/- 12.1 (mean +/- SD) primary colonies. Cells from a single blast colony were separated into two aliquots and replated in secondary methylcellulose cultures containing SCF and IL-7 for B cell lineage and SCF, IL-3, G-CSF, GM-CSF and EPO for myeloid lineage. Next, cells from five to ten primary blast colonies were cultured again in embryonal thymus (25 Gy irradiated). One aliquot of blast colonies in a primary culture contained four colony forming units (CFU) of granulocytes, erythroblasts, macrophages and megakaryocytes, eight CFU-granulocytes and macrophages, and 28 BFU-E in a representative secondary myeloid culture. Another aliquot formed a few B cell colonies (2-10) in a secondary B cell culture. B lymphoid colonies were composed of blast-like cells with B-220 antigen. T cells in a secondary T cell culture consisted of 16% L3T4+, 16% CD8+ and 11% CD3+ of bone marrow origin in the thymus. From these results, we concluded that cells in the primary colonies from Sca-1+Lin- hematopoietic stem cells could differentiate into B cell, T cell and myeloid lineages.

Animals↗

PubMed1996

The effects of dopamine D1 and D2 receptor antagonists on the rewarding effects of delta 1 and delta 2 opioid receptor agonists in mice.

The effects of the dopamine D1 antagonist SCH23390 and the D2 antagonist sulpiride on the rewarding effects of delta opioid receptor agonists were examined in mice. Both [D-Pen2, Pen5]enkephalin (DPDPE, 1-15 nmol, ICV), a selective delta 1 opioid receptor agonist, and [D-Ala2]deltorphin II (DELT, 0.5-5 nmol, ICV), a selective delta 2 opioid receptor agonist, produced a dose-dependent place preference in mice. The DPDPE (15 nmol, ICV)-induced place preference was abolished by BNTX (0.5 mg/kg, SC), a delta 1 opioid receptor antagonist, but not by NTB (0.5 mg/kg, SC), a delta 2 opioid receptor antagonist. In contrast, the DELT (5 nmol, ICV)-induced place preference was antagonized by NTB, but not BNTX. Pretreatment with SCH23390 (3 micrograms/kg, SC) abolished the DPDPE-induced place preference, but not affect the DELT-induced place preference. Moreover, pretreatment with sulpiride (40 mg/kg, SC) did not modify the place preference induced by DPDPE or DELT. In the present study, we found that the activation of both central delta 1 and delta 2 opioid receptors produced rewarding effects. Furthermore, these results suggest that the rewarding effects of delta 1 opioid receptor agonist may be produced through activation of the central dopaminergic system, especially dopamine D1 receptors, whereas the rewarding effects of delta 2 opioid receptor agonists may be produced by some other mechanism(s).

Animals↗

PubMed1996

Diazepam pretreatment suppresses morphine withdrawal signs in the mouse.

The effect of diazepam on the development of physical dependence on morphine and on the naloxone-precipitated increase in cortical NA turnover were investigated in mice. Co-administration of diazepam (1-4 mg/kg, i.p.) during chronic morphine treatment suppressed the expression of naloxone (3 mg/kg, s.c.)-precipitated withdrawal signs (jumping, exploratory rearing and weight loss). However, a single injection of diazepam (4 mg/kg, i.p.) in morphine-dependent mice did not affect the expression of naloxone-precipitated withdrawal signs. The 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) level and noradrenaline (NA) turnover (MHPG/NA) in the cerebral cortex were increased by naloxone (3 mg/kg) challenge. These increases in the cortical MHPG level and NA turnover were significantly prevented by co-administration of diazepam (4 mg/kg, i.p.) during chronic morphine treatment. These findings suggest that the co-administration of diazepam during chronic morphine treatment may prevent some neurochemical changes in the central noradrenergic system during chronic morphine treatment, and may suppress the development of physical dependence on morphine. Therefore, the inhibitory action of GABA via benzodiazepine binding sites may play an important role in the development of physical dependence on morphine.

Adrenergic alpha-Agonists↗

PubMed1996

Formalin- and carrageenan-induced inflammation attenuates place preferences produced by morphine, methamphetamine and cocaine.

Morphine-, methamphetamine- and cocaine-induced place preferences under inflammation produced by unilateral injections of 2.5% formalin (50 microliters) and 1% carrageenan (100 microliters) into the hind paw were examined in rats. Formalin and carrageenan reduced the paw pressure threshold, and this hyperalgesia lasted for 9 and 13 days, respectively. Morphine-, cocaine- and methamphetamine-induced place preferences were significantly attenuated in inflamed groups as compared with the respective noninflamed groups. However, indomethacin failed to produce a place preference in either group. Furthermore, the morphine-induced place preference in the inflamed group gradually recovered to the respective control level as the inflammation healed. These results suggest that the rewarding effects of morphine, cocaine and methamphetamine are attenuated in the presence of inflammatory nociception.

Animals↗

PubMed1996

Abnormal modulation of cholinergic neurotransmission by opioid in hyperresponsive bronchus of rats.

1. The electrical field stimulation (EFS)-induced bronchoconstriction in vitro in rats challenged by DNP-Ascaris antigen was significantly greater than that in normal rats. 2. Morphine inhibited the EFS-induced bronchoconstriction in normal rats. Whereas the inhibition of EFS-induced bronchoconstriction by the opioid was little, if any, in the DNP-Ascaris-challenged rats. 3. These findings suggest that dysfunction of presynaptic inhibitory modulation through the opioid receptor may take place in the airways of DNP-Ascaris-challenged rats.

Acetylcholine↗

PubMed1996

Effect of the highly selective and nonpeptide delta opioid receptor agonist TAN-67 on the morphine-induced place preference in mice.

The effect of 2-methyl-4a alpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12, 12a alpha-octahydroquinolino [2,3,3,-g]isoquinoline (TAN-67), a selective non-peptide delta opioid receptor agonist, on the morphine-induced place preference was examined in mice. Morphine (1-5 mg/kg, s.c.) produced a dose-related place preference in mice. In contrast, administration of TAN-67 (5-20 mg/kg, s.c.) did not result in a preference for either the drug- or vehicle-associated place. When TAN-67 (5-20 mg/kg, s.c.) was coadministered with morphine (1 mg/kg, s.c.), the morphine-induced place preference was enhanced dose dependently, and this effect of TAN-67 was suppressed by the pretreatment with naltrindole (1 mg/kg, s.c.), a nonselective delta opioid receptor antagonist, 7-benzylidenenaltrexone (0.05 and 0.5 mg/kg, s.c.), a selective delta 1 opioid receptor antagonist, and naltriben (0.05 and 0.5 mg/kg, s.c.), a selective delta 2 opioid receptor antagonist. In biochemical study, morphine (1 mg/kg, s.c.) or TAN-67 (20 mg/kg, s.c.) alone did not modify dopamine turnover in the limbic forebrain. Coadministration of TAN-67 (20 mg/kg, s.c.) with morphine (1 mg/kg, s.c.) increased DA turnover in the limbic forebrain. This increase in DA turnover in the limbic forebrain was suppressed by pretreatment with naltrindole (1 mg/kg, s.c.) or 7-benzylidenenaltrexone (0.5 mg/kg, s.c.), but not by naltriben (0.5 mg/kg, s.c.). Our results demonstrate that coadministration of TAN-67 with morphine enhances the morphine-induced place preference via activation of both delta 1 and delta 2 opioid receptors, suggesting that both delta 1 and delta 2 opioid receptors may modulate the morphine-induced rewarding effect. In addition, we also found that although both delta 1 and delta 2 opioid receptors may be implicated in the modulation of rewarding effect of morphine, the mechanisms involved may be different for each receptor subtypes, i.e., mu-delta 1 interaction may mainly modulate the rewarding effect of morphine by enhancing neurotransmission of mesolimbic dopamine neurons, although modulation by mu-delta 2 opioid receptor interaction may involve some other dopamine-independent mechanisms.

Analgesics↗

PubMed1996

Involvement of NO-ergic neural pathway in reflex tracheal dilatation during bronchoconstriction in guinea pigs.

The involvement of NOergic nerve in vagal reflex-mediated tracheal dilatation during bronchoconstriction was investigated using the guinea pig in vivo tracheo-bronchi separated preparation. Inhalation of 0.01% histamine to the bronchial site induced a biphasic, vagal reflex tracheal response, i.e., constriction followed by dilatation slightly after bronchial constriction. The reflex tracheal dilatation was inhibited by 49% by local treatment of the tracheal site with 1% propranolol. The residual dilatation in the presence of atropine and propranolol was significantly inhibited by 1% oxyhemoglobin or 1% carboxy-PTIO, NO scavengers. Cyclic GMP content in the tissue of the tracheal site during the reflex tracheal dilatation significantly increased. The increase in cyclic GMP was reduced by treatment of the tracheal site with 1% N omega-nitro-L-arginine methyl ester. These results support a hypothesis that reflex tracheal dilatation during bronchoconstriction may be mediated by not only adrenergic but also NOergic nerves in guinea pigs.

Administration, Inhalation↗