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Biomedical subjects

M Funada

Publications and source records attributed to M Funada.

At least 37 records · Page 2Linked to original sources
PubMed1994

Effects of a lipopolysaccharide from Pantoea agglomerans on the cocaine-induced place preference.

A lipopolysaccharide from Pantoea agglomerans (LPSp) was purified, and its effect on the cocaine-induced place preference was examined in rats. Cocaine (4 mg/kg, i.p.) produced a significant place preference. Administration of LPSp (5-1000 micrograms/kg, i.p.) alone resulted in neither preference nor aversion for either the drug- or saline-associated place. However, pretreatment with LPSp (500 and 1000 micrograms/kg, i.p.) abolished the place preference that had been induced by cocaine. Furthermore, treatment with LPSp (500 micrograms/kg, i.p.) abolished cocaine (20 mg/kg, i.p.)-induced locomotor enhancement in mice. These results suggest that while LPSp itself may possess neither reinforcing nor locomotor enhancing effects, it blocks both the reinforcing and the locomotor enhancing effects of cocaine. Therefore, LPSp might be useful in pharmacotherapy for prevention of recurrent cocaine abuse.

Animals↗
PubMed1994

Role of beta-adrenoceptors in the expression of morphine withdrawal signs.

The effects of intracerebroventricular (i.c.v.) pretreatment with the noradrenergic neurotoxin DSP-4 and beta 1- and beta 2-adrenoceptor antagonists on the expression of morphine withdrawal signs were investigated in mice. Mice were chronically treated with morphine (8-45 mg/kg, s.c.). Several withdrawal signs were observed following naloxone challenge in morphine-dependent mice which had been pretreated with vehicle. Treatment with DSP-4 before the naloxone challenge suppressed the expression of morphine withdrawal signs, including jumping and "wet dog" shakes. Similarly, pretreatment with the beta 1-antagonist atenolol significantly reduced the incidence of naloxone-precipitated jumping and "wet dog" shakes. However, pretreatment with the beta 2-antagonist ICI118,551 suppressed the expression of "wet dog" shakes, but not that of jumping. These findings suggest that the central noradrenergic system may mediate the expression of withdrawal signs. The blocking effects of beta-antagonists indicate that naloxone-precipitated jumping may be mediated predominantly by beta 1-adrenoceptors, while naloxone-precipitated "wet dog" shakes may be mediated by both beta 1- and beta 2-adrenoceptors.

Adrenergic Agents↗
PubMed1993

Effect of cyclosporine A on the morphine-induced place preference.

The effect of pretreatment with cyclosporine A, an immunosuppressant, on the morphine-induced place preference was examined in ddY and mu1 opioid receptor-deficient CXBK mice. Morphine produced a significant preference for the drug-associated place in ddY and CXBK mice. Administration of cyclosporine A alone to ddY and CXBK mice did not result in either preference or aversion for either the drug- or vehicle-associated place. On the other hand, pretreatment with cyclosporine A suppressed the place preference induced by morphine in ddY mice in a dose-dependent manner. However, in CXBK mice, pretreatment with cyclosporine A did not affect the morphine-induced place preference. These results suggest that cyclosporine A suppresses the reinforcing effect induced by morphine, and that this suppression by cyclosporine A may be mediated by mu1 opioid receptors.

Animals↗
PubMed1993

Modification of morphine-induced locomotor activity by pertussis toxin: biochemical and behavioral studies in mice.

The effect of pertussis toxin (PTX) on the locomotor-enhancing action of systemic and intracerebroventricular (i.c.v.) morphine was investigated in mice. Mice were i.c.v. injected with either PTX (0.25 and 0.5 micrograms) or saline as a control. The s.c. (5-20 mg/kg) and i.c.v. (7-30 nmol) administration of morphine produced a dose-related locomotor-enhancing action in control mice. The peak effect of morphine (30 nmol, i.c.v.)-induced hyperlocomotion was observed 90 min after the morphine injection. At the same time, morphine significantly increased dopamine (DA) metabolism in the limbic forebrain (nucleus accumbens and olfactory tubercle). Similarly, the selective mu-opioid receptor agonist [D-Ala2,N-MePhe4,Gly-ol5]enkephalin (DAGO, 4 nmol, i.c.v.) also significantly increased locomotor activity and DA metabolism in the limbic forebrain. Both morphine- and DAGO-induced hyperlocomotion and elevation of DA turnover were antagonized by pretreatment with the mu antagonist beta-funaltrexamine (beta-FNA). These results suggest that the locomotor-enhancing action of morphine results from the activation of central mu-opioid receptors, and that the activation of the mesolimbic DA system may be involved in the expression of morphine-induced hyperlocomotion in mice. Furthermore, pretreatment with PTX (0.5 micrograms, i.c.v., 6 days prior to the testing) significantly reduced hyperlocomotion and elevation of DA turnover in the limbic forebrain which had been induced by administrations of morphine (30 nmol, i.c.v.) and DAGO (4 nmol, i.c.v.). These findings suggest that the central PTX-sensitive GTP-binding protein (G-protein) mechanism may play an important role in opioids-induced locomotor-enhancing action. Furthermore, the activation of mesolimbic DA transmission by mu-opioid agonists may also be mediated by a PTX-sensitive G-protein mechanism in mice.

Analgesics↗
PubMed1993

Morphine-induced place preference in the CXBK mouse: characteristics of mu opioid receptor subtypes.

The role of mu opioid receptor subtypes, mu 1 and mu 2, in morphine-conditioned place preference was examined using ddY and mu 1 opioid receptor-deficient CXBK mice. In ddY mice, the mu receptor agonist morphine caused a dose-related preference for the drug-associated place, but the kappa agonist U-50,488H produced a dose-related place aversion. These results demonstrated that the mouse is available for place preference conditioning using opioids. Under this condition, the influence of pretreatment with the selective mu 1 opioid receptor antagonist naloxonazine on morphine-induced place preference was investigated in ddY mice. Although pretreatment with the selective mu 1 antagonist naloxonazine (35 mg/kg, s.c.) did not modify the morphine-induced place preference, pretreatment with the selective mu antagonist beta-funaltrexamine (beta-FNA 10 mg/kg, s.c.) eliminated the appetitive effect of morphine. Furthermore, morphine (1-5 mg/kg, s.c.) produced a dose-related preference for the drug-associated place in CXBK mice. These findings suggest that the morphine-induced conditioned place preference may be mediated by naloxonazine-insensitive sites (mu 2 opioid receptors). In addition, chronic infusion of the dopamine D1 antagonist SCH23390 (1.0 mg/kg/day) during the conditioning sessions eliminated the morphine-induced place preference in CXBK mice. Similarly, morphine combined with naloxonazine failed to produce the place preference in ddY mice chronically treated with SCH23390. The blocking effect of SCH23390 on the morphine-conditioned place preference suggests that mu 2 receptors may regulate the dopaminergic system, especially dopamine D1 receptors, and are also involved in the reinforcing effects of morphine.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1993

Effect of pretreatment with pertussis toxin on the development of physical dependence on morphine.

The effect of intracerebroventricular (i.c.v.) pretreatment with pertussis toxin (PTX) on the development of physical dependence on morphine was investigated in mice. Twenty four hours after PTX (0.5 microgram, i.c.v.) or vehicle pretreatment, the mice were chronically treated with morphine (8-45 mg/kg, s.c.) for 5 days. Several withdrawal signs were observed following naloxone challenge in morphine-dependent mice which had been pretreated with vehicle. In addition, 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and noradrenaline (NA) turnover (MHPG/NA) levels in the cerebral cortex were increased following naloxone challenge in morphine-dependent mice. These findings indicate that activation of the central noradrenergic system may mediate the expression of some withdrawal signs. In contrast, pretreatment with PTX attenuated the naloxone-precipitated withdrawal signs in morphine-dependent mice. The incidence of withdrawal signs such as jumping, "wet dog" shakes, and rearing was significantly reduced by PTX pretreatment. PTX pretreatment also prevented the naloxone-precipitated increases in MHPG concentration and NA ratio (MHPG/NA) in the cerebral cortex, suggesting that central PTX-sensitive GTP-binding proteins (G-proteins) may be involved in the elevation of NA transmission in the cortex which projects from the locus coeruleus (LC) during morphine withdrawal. The blocking effects of PTX on the behavioral and biochemical changes after withdrawal suggest that central PTX-sensitive G-proteins (Gi/Go) may play an important role in the development of physical dependence on morphine.

Animals↗
PubMed1993

Activation of central ATP-sensitive potassium channels produces the antinociception and spinal noradrenaline turnover-enhancing effect in mice.

ICV cromakalim, a K+ channel opener, produced antinociception. This effect was completely antagonized by ICV glibenclamide, a selective adenosine triphosphate-sensitive K+ channel (KATP channel) blocker. Furthermore, direct opening of central KATP channels by ICV cromakalim increased the spinal noradrenaline (NA) turnover. On the other hand, the antinociception induced by ICV morphine (mu opioid agonist), but not ICV U-50,488H (kappa opioid agonist) was markedly potentiated by cromakalim. These findings suggest that the opening of central KATP channels may elicit the antinociceptive effect and activate the descending NAergic pathway, and central KATP channels play an important role as a modulator of the antinociception induced by mu agonists but not kappa agonists.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1993

Involvement of delta-opioid receptors in the effects of morphine on locomotor activity and the mesolimbic dopaminergic system in mice.

Naltrindole (NTI) and naltriben (NTB), a benzofuran derivative of NTI, were recently synthesized as highly selective delta-opioid receptor antagonists. Both NTI and NTB failed to suppress the antinociceptive effect induced by morphine. In contrast, both NTI and NTB significantly suppressed the morphine-induced hyperlocomotion and increase in turnover of dopamine (DA) in the mouse limbic forebrain. These results suggest that delta-opioid receptors play, at least in part, a role in the morphine-induced hyperlocomotion and excitation of mesolimbic DA systems, but not antinociception.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Blockade of the morphine-induced increase in turnover of dopamine on the mesolimbic dopaminergic system by kappa-opioid receptor activation in mice.

Activation of central mu opioid receptors by treatment with systemic morphine elevates 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) levels without changing dopamine (DA) and 5-hydroxytryptamine (5-HT: serotonin) steady-state levels in the mouse limbic forebrain (including nucleus accumbens and olfactory tubercle). Pretreatment with systemic U-50,488H, a selective kappa agonist, could dose-dependently block the morphine-induced increase in turnover of DA. This blocking action by treatment with U-50, 488H was completely reversed by nor-binaltorphimine (nor-BNI), a selective kappa antagonist. On the other hand, U-50,488H did not affect the enhancement of 5-HT turnover induced by morphine. These findings suggest that kappa receptor activation can inhibit the mu agonist-induced activation of mesolimbic DA pathway but not ascending 5-HT pathway.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1993

Blockade of morphine reward through the activation of kappa-opioid receptors in mice.

The effects of systemic (s.c.) treatment with the kappa-agonists U-50,488H and E-2078 (a stable dynorphin analog) on the morphine-induced place preference were examined in mice. Morphine (s.c.) caused a dose-related preference for the drug-associated place; the effects at doses of 3 and 5 mg/kg were significant. On the other hand, U-50,488H or E-2078 produced a dose-related conditioned place aversion. Both U-50,488H (1 mg/kg, s.c.) and E-2078 (0.1 mg/kg, s.c.) induced a slight, nonsignificant place aversion. Pretreatment with U-50,488H (1 mg/kg) abolished the morphine (3 mg/kg)-induced place preference. The morphine-induced place preference was also significantly decreased by pretreatment with E-2078 (0.1 mg/kg). The inhibitory effects of the kappa-agonists were antagonized by the kappa-antagonist nor-binaltorphimine (nor-BNI; 3 mg/kg, s.c.). In contrast, pretreatment with U-50,488H did not affect the place preference induced by the dopamine (DA) receptor agonist apomorphine (1 mg/kg, s.c.). In addition, morphine (3 mg/kg, s.c.) significantly increased the levels of the DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the limbic forebrain (nucleus accumbens and olfactory tubercle) but not in the striatum, implying that activation of the mesolimbic DA system may play an important role in the morphine-induced place preference in mice. Pretreatment with U-50,488H significantly reduced the morphine-induced elevation of DA metabolites in the limbic forebrain.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1993

Effects of kappa-agonist on the antinociception and locomotor enhancing action induced by morphine in mice.

The antinociception of intracerebroventricular injection (i.c.v.) of morphine was markedly abolished by pretreatment with naloxonazine (micro 1-antagonist), s.c.; beta-funaltrexamine (micro 1/micro 2-antagonist), i.c.v.; DSP-4 (noradrenaline neurotoxin), s.c.; or p-chlorophenylalanine (serotonin synthesis inhibitor), s.c. in the mouse 55 degrees C hot-plate assay. Pretreatment with nor-binaltorphimine (kappa-antagonist), i.c.v. or PCPA, s.c. drastically blocked the kappa-agonist U-50,488H-induced supraspinal antinociception. These findings indicate either noradrenergic or serotonergic involvement in the mediation of the antinociceptio of i.c.v.-morphine through mu-receptors. On the contrary, the antinociception of i.c.v.- U-50,488H through kappa-receptors appears to depend on the serotonergic but not noradrenergic systems. The antinociceptive interaction between the i.c.v.-morphine and -U-50,488H was an additive effect. On the other hand, i.c.v.-morphine dose-dependently increased the locomotion in mice, and this hyperlocomotion of morphine was drastically blocked by pretreatment with either beta-funaltrexamine, i.c.v. or 6-hydroxydopamine (dopamine depletor), i.c.v. I.c.v.-U-50,488H dose-dependently reduced the increasing locomotion of i.c.v.-morphine, but not that of s.c.-apomorphine (dopamine receptor agonist), and this effect of U-50,488H was completely reversed by pretreatment with nor-binaltorphimine, i.c.v. These results suggest that coadministration of kappa-agonists can suppress the dopamine-related hyperlocomotion of mu-agonists without decreasing the anti-nociception of mu-agonists in mice.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1992

[Effects of dietary proteins on analgesic activity of tolerance and physical dependence on morphine in rats].

Effects of dietary proteins such as casein and egg albumin on analgesic activity of, tolerance to and physical dependence on morphine in rats were examined. There was no difference in analgesic activity after acute administration of morphine 10 mg/kg, s.c. between rats treated with casein food or egg albumin food and normal food for 5 or 21 days. The development of tolerance to morphine analgesia in rats treated with albumin food but not with casein food was suppressed during daily morphine 10 mg/kg, s.c. on 5 consecutive days. Rats were treated with casein or albumin food mixed with morphine (0.5 mg/g of food) for 5 days. Morphine intake in rats treated with albumin food was significantly decreased as compared to that with morphine admixed casein or normal food. Body weight loss by naloxone in morphine-dependent rats was significantly less in both casein food and albumin food groups than in the normal food group. These results suggest that chronic dietary treatment with albumin may produce a partial inhibition of development of tolerance to morphine analgesia and that with casein may attenuate morphine withdrawal manifestation in rats.

Analgesics, Opioid↗
PubMed1991

Pertussis toxin abolishes mu- and delta-opioid agonist-induced place preference.

The effects of i.c.v. treatment with pertussis toxin (PTX) on the motivational effect of opioid agonists were examined in mice. Morphine (0.1-10 nmol, i.c.v.), [D-Ala2, N-MePhe4, Gly-ol5]enkephalin (DAGO, 0.001-0.1 nmol, i.c.v.), a selective mu-opioid receptor agonist, and [D-Pen2, D-Pen5]enkephalin (DPDPE, 1-15 nmol, i.c.v.), a selective delta-opioid receptor agonist, produced a dose-related place preference in mice. Administration of PTX (0.5 micrograms, i.c.v.) to mice resulted in no preference for either the drug- or vehicle-associated place. Pretreatment with PTX abolished the place preferences induced by DAGO (0.1 nmol), morphine (10 nmol) and DPDPE (15 nmol). These findings demonstrate that the appetitive effects of opioids result from the activation of central mu- and delta-receptors, and suggest that PTX-sensitive GTP-binding proteins in the central nervous system may be involved in the motivational effects of mu- and delta-opioid agonists.

Animals↗
PubMed1989

Bilateral macular coloboma associated with progressive atrophy of the peripheral retina.

An 11-year-old girl with poor visual acuity since birth was found to have nearly complete defects of the retinochoroidal tissue in the central areas of both fundi and almost normal peripheral retinas. Her parents were first cousins. At age 24, the patient reported night blindness. An examination showed geographic atrophy of the peripheral retina and stationary macular lesions in both eyes. Her condition appeared to be a rare case of bilateral macular coloboma associated with progressive peripheral retinal atrophy.

Atrophy↗
PubMed1987

Effects of aldose reductase inhibitor (M79175) on ERG oscillatory potential abnormalities in streptozotocin fructose-induced diabetes in rats.

The effects of an aldose reductase inhibitor (M79175) on electroretinogram (ERG) oscillatory potential abnormalities was studied in rats with streptozotocin fructose-induced diabetes. The ERG oscillatory potential was recorded under scotopic conditions without general anesthesia in the diabetic rats, before and 4, 8 and 12 weeks after administration of M79175. The ERG tracings were analyzed for peak latencies, peak intervals and amplitudes; the peak latencies and intervals were prolonged and the amplitudes were reduced in untreated diabetic rats, but the prolongation of the peak latencies and intervals were suppressed in diabetic rats receiving M79175. The amplitudes were reduced in the treated rats as in the untreated rats. The results of this investigation suggest that M79175 is effective to suppress progression of diabetic retinopathy in its early stage.

Aldehyde Reductase↗
PubMed1985

Metachronous bilateral adrenal neuroblastoma.

A boy with bilateral adrenal neuroblastoma was presented. The left adrenal neuroblastoma was found when he was at 5 years of age and was curatively excised. The right adrenal neuroblastoma was found when he was at 13 years of age and also was totally excised. The authors consider that the case presented is an extremely rare, metachronous primary bilateral adrenal neuroblastoma, reflecting the multicentric origin of neuroblastoma.

Adolescent↗