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Biomedical subjects

M Misawa

Publications and source records attributed to M Misawa.

At least 109 records · Page 6Linked to original sources
PubMed1995

Interaction between discriminative stimulus effects of cocaine and morphine.

We recently demonstrated that combining cocaine and morphine could enhance their reinforcing effects which may be mediated by the dopaminergic system. In the present study, the effects of cocaine and morphine on the discriminative stimulus effects of morphine and cocaine, respectively, were examined. Furthermore, dopaminergic mediation in the discriminative stimulus effects of morphine was also examined. Pretreatment with 1.0 or 3.0 mg/kg morphine shifted the dose-response curve for cocaine to the left, and 3.0 mg/kg morphine significantly potentiated the discriminative stimulus effects of cocaine. On the other hand, neither 1.25 nor 2.5 mg/kg cocaine affected the discriminative stimulus effects of morphine. These results suggest that potentiation of the discriminative stimulus effects of cocaine by morphine may reflect the enhancement of reinforcing effects in the combination of cocaine and morphine. Furthermore, neither SCH23390 (D1-receptor antagonist) nor haloperidol (D2-receptor antagonist) affects the discriminative stimulus effects of morphine, while combining these drugs slightly attenuated the effects of morphine. Thus, another neurotransmitter rather than dopamine may play an important role in the discriminative stimulus effects of morphine. Therefore, the discriminative stimulus effects of morphine are apparently not potentiated by cocaine, unlike those of reinforcing effects.

Animals↗
PubMed1995

Effects of nifedipine on physical dependence on barbital or diazepam in rats.

The effects of nifedipine on the development of physical dependence on barbital and diazepam in rats were examined using the drug-admixed food method. Rats were chronically treated with either barbital- or barbital in combination with nifedipine-admixed food for 28 days, and with either diazepam- or diazepam in combination with nifedipine-admixed food for 26 days, on schedules of gradually increasing doses of barbital or diazepam. Withdrawal was conducted by substituting normal food for drug-admixed food on the last day of the treatment. Co-administration of nifedipine with barbital potentiated weight loss and withdrawal scores after the termination of barbital treatment. However, the withdrawal signs after the termination of diazepam treatment were not affected by co-administration of nifedipine with diazepam. These results suggest that nifedipine potentiates the development of physical dependence on barbital but not diazepam. It is known that co-administration of dihydropyridine derivative nitrendipine suppresses the development of physical dependence on ethanol. Basing on the differences in sensitivity of central depressants, barbiturates, benzodiazepines and ethanol, to three types of voltage-dependent Ca2+ channels, such as L-, N- and T-types studied so far, the development of physical dependence on central depressants may be modified differently by L-type Ca2+ channel blockers, corresponding to respective depressants.

Analysis of Variance↗
PubMed1995

Toxicodynamic analysis of cough and inflammatory reactions by angiotensin-converting enzyme inhibitors in guinea pig.

Angiotensin-converting enzyme (ACE) inhibitors are one of the first drugs of choice for the treatment of hypertension. However, there have been many reports of persistent chronic dry cough and inflammatory skin reactions (rash and/or angioedema, etc.) induced by ACE inhibitors. In this study, in order to evaluate the cough and inflammatory reaction, we measured the number of citric acid-induced coughs and the intradermal inflammation with ovalbumin in guinea pigs consecutively treated with ACE inhibitors (lisinopril, enalaprilat and imidapril) for 3 days. The number of citric acid-induced coughs and the inflammatory responses were significantly enhanced by treatment with lisinopril and enalaprilat, whereas imidapril produced no change in either response. These results correspond to the frequency of adverse effects in clinical practice, which suggests that imidapril has the least ability to induce the inflammatory skin response and cough. Furthermore, the enhancement produced by the ACE inhibitors in the number of coughs and the inflammatory responses were significantly reduced by pretreatment with indomethacin (prostaglandin synthesis inhibitor). This finding suggests that PGs at least participate in the mechanism for ACE inhibitor-induced cough and inflammatory skin response.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Modification of mu-opioid agonist-induced locomotor activity and development of morphine dependence by diabetes.

We examined the locomotor-enhancing action of mu-opioid receptor agonists, such as morphine and [D-Ala2, N-MePhe4, Gly-ol5]enkephalin (DAMGO), and physical dependence on morphine in diabetic and nondiabetic mice. Morphine (5-20 mg/kg, s.c.) and DAMGO (1-4 nmol, i.c.v.) had a dose-dependent locomotor-enhancing effect in both nondiabetic and diabetic mice. The locomotor-enhancing effects of morphine and DAMGO were significantly less in diabetic mice than in nondiabetic mice, and were significantly reduced after pretreatment with either beta-funaltrexamine (20 mg/kg, s.c.), a selective mu-opioid receptor antagonist, or naloxonazine (35 mg/kg, s.c.), a selective mu1-opioid receptor antagonist. Both diabetic and nondiabetic mice were chronically treated with morphine (8-45 mg/kg, s.c.) for 5 days. During this treatment, neither diabetic nor nondiabetic mice showed any signs of toxicity. After morphine treatment, withdrawal was precipitated by injection of naloxone (0.3-10 mg/kg, s.c.). Several withdrawal signs, such as weight loss, diarrhea, ptosis, jumping and body shakes, were observed after naloxone challenge in morphine-dependent nondiabetic mice. Although morphine-dependent diabetic mice showed greater weight loss than nondiabetic mice, the incidence of jumping and body shakes after naloxone challenge in diabetic mice were lower than that in nondiabetic mice. These results suggest that diabetic mice are selectively hyporesponsive to mu1-opioid receptor-mediated locomotor enhancement. Furthermore, diabetes may affect mu1-opioid receptor-mediated naloxone-precipitated signs of withdrawal from physical dependence on morphine.

Animals↗
PubMed1995

Effect of diabetes on the morphine-induced inhibition of gastrointestinal transit.

The effect of diabetes on the morphine-induced inhibition of gastrointestinal transit was examined in mice. Morphine dose-dependently inhibited gastrointestinal transit after s.c. administration in both non-diabetic mice and diabetic mice. There was no significant difference between the ED50 values for this antitransit effect of morphine in non-diabetic and diabetic mice. The gastrointestinal antitransit effect of morphine was significantly antagonized by pretreatment with beta-funaltrexamine (40 mg/kg, s.c.), a selective mu-opioid receptor antagonist, in both non-diabetic and diabetic mice. However, pretreatment with naloxonazine (35 mg/kg, s.c.), a selective mu 1-opioid receptor antagonist, had no effect on the antitransit properties of morphine. These results suggest that diabetes failed to alter the mu 2-opioid receptor-mediated antitransit effect of morphine.

Animals↗
PubMed1994

Attenuation of the discriminative stimulus properties of cocaine by delta-opioid receptor antagonists.

The effects of selective delta-opioid receptor antagonists on the discriminative stimulus properties of cocaine were examined in rats trained to discriminate between cocaine (10 mg/kg) and saline. Pretreatment with naltrindole (a non-selective delta-opioid receptor antagonist) and naltriben (a selective delta 2-opioid receptor antagonist), but not 7-benzylidenenaltrexone (a selective delta 1-opioid receptor antagonist), significantly attenuated the discriminative stimulus properties of cocaine. Naltrindole and naltriben attenuated the discriminative stimulus properties of doses of cocaine lower than the training dose. Although the effects produced by the training dose were not changed, our finding may have some bearing on the relative importance of the role of delta-opioid (especially delta 2-opioid) receptors in the discriminative stimulus properties of cocaine.

Animals↗
PubMed1994

Effects of diabetes on the morphine-induced Straub tail reaction in mice.

The effects of diabetes on the morphine-induced Straub tail reaction were examined in mice. The Straub tail reaction induced by s.c. administration of morphine was significantly less in diabetic mice than in non-diabetic mice. The morphine-induced Straub tail reaction was significantly reduced following pretreatment with beta-funaltrexamine, a selective mu-opioid receptor antagonist, in both diabetic and non-diabetic mice. Furthermore, the morphine-induced Straub tail reaction was also significantly reduced in both diabetic and non-diabetic mice following pretreatment with naloxonazine, a selective mu1-opioid receptor antagonist. These results suggest that mice with diabetes are hypo-responsive to mu1-opioid receptor-mediated Straub tail reaction.

Animals↗
PubMed1994

Effects of diabetes on spontaneous locomotor activity in mice.

Spontaneous locomotor activity in diabetic mice was significantly greater than that in non-diabetic mice. Haloperidol and SCH23390, a selective dopamine D1-receptor antagonist, significantly reduced spontaneous locomotor activity in diabetic mice, but not in non-diabetic mice. Spontaneous locomotor activity in diabetic mice was also reduced by pretreatment with naltrindole, a selective delta-opioid receptor antagonist, and 7-benzylidenenaltrexone, a selective delta1-opioid receptor antagonist. The rate of dopamine turnover in the limbic forebrain in diabetic mice was significantly higher than that in non-diabetic mice. These findings suggest that the enhanced spontaneous locomotor activity in diabetic mice may result from increased dopamine neurotransmission, which might be due to an increase in dopamine release in mesolimbic dopamine systems. The increased dopamine neurotransmission in diabetic mice may also be due to the up-regulation of delta-opioid receptor-mediated functions.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Antitussive effect of dihydroetorphine in mice.

The present study examined the opioid receptors involved in the antitussive effect of dihydroetorphine in mice. Dihydroetorphine suppressed coughs dose dependently at doses between 0.1-1 micrograms/kg i.p. Blockade of mu-opioid receptors by pretreatment with beta-funaltrexamine significantly reduced the antitussive effect of dihydroetorphine. Furthermore, the antitussive effect of dihydroetorphine was also antagonized by nor-binaltorphimine, a kappa-opioid receptor antagonist. However, pretreatment with naltrindole, a delta-opioid receptor antagonist, did not affect the antitussive effect of dihydroetorphine. These results indicate that the antitussive effect of dihydroetorphine is mediated by the activation of mu-opioid receptors and of kappa-opioid receptors, but not delta-opioid receptors.

Alkylating Agents↗
PubMed1994

The role of dopamine D1-receptors in morphine-induced hyperlocomotion in mice.

The effects of treatment with dopamine (DA) D1-agonist SKF38393 and D2-agonist quinpirole on morphine-induced hyperlocomotion were investigated in mice. Morphine-induced hyperlocomotion was increased by approximately 2.0-fold in SKF38393 (10 nmol, i.c.v.)-treated mice. Pretreatment with SCH23390 antagonized the enhancing effect of SKF38393. In contrast, pretreatment with quinpirole (10 nmol, i.c.v.) reduced morphine-induced hyperlocomotion. Morphine significantly increased DA metabolite levels, 3,4-dihydroxyphenylacetic acid and homovanillic acid in the limbic forebrain (nucleus accumbens and olfactory tubercle). This elevation of DA metabolites by treatment with morphine was not modified by the co-administration of SKF38393. These results suggest that the activation of D1-receptors in the limbic forebrain may enhance the expression of morphine-induced hyperlocomotion.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1994

Antinociceptive effect of L-arginine in diabetic mice.

The antinociceptive effect of L-arginine in streptozotocin-induced diabetic mice was examined. Although s.c. administration of L-arginine produced a dose-dependent inhibition of the tail-flick response in both non-diabetic and diabetic mice, the antinociceptive response was greater in diabetic mice than in non-diabetic mice. The antinociceptive effects of L-arginine in both diabetic and non-diabetic mice were significantly antagonized by s.c. administration of naltrindole, a selective delta-opioid receptor antagonist. However, neither beta-funaltrexamine, a selective mu-opioid receptor antagonist, nor nor-binaltorphimin ++, a selective kappa-opioid receptor antagonist, significantly affected the antinociceptive effect of L-arginine in diabetic and non-diabetic mice. These results suggest that L-arginine produces a marked antinociceptive effect in diabetic mice through the activation of delta-opioid receptors.

Analgesics↗
PubMed1994

Antitussive effect of [Met5]enkephalin-Arg6-Phe7 in mice.

We examined the effect of [Met5]enkephalin-Arg6-Phe7 (MEAP) on the capsaicin-induced cough reflex in mice. Intracerebroventricular administration of MEAP significantly decreased the number of coughs in a dose-dependent manner. The antitussive effect of MEAP was blocked by nor-binaltorphimine, a selective kappa-opioid receptor antagonist. However, beta-funaltrexamine, a mu-opioid receptor antagonist, had no effect on the antitussive effect of MEAP. On the other hand, the antinociceptive effect of MEAP, as determined in the tail-flick test, was blocked by both nor-binaltorphimine and beta-funaltrexamine. Naltrindole, a delta-opioid receptor antagonist, had no effect on either the antitussive effect or the antinociceptive effect of MEAP. These data suggest that MEAP exerts its antitussive effect in mice through the stimulation of kappa-opioid receptors, whereas the antinociceptive effect of MEAP is mediated through the simulation of both kappa- and mu-opioid receptors.

Animals↗
PubMed1994

Involvement of delta 1-opioid receptor antagonism in the antitussive effect of delta-opioid receptor antagonists.

The effects of 7-benzylidenenaltrexone (BNTX), a selective delta 1-opioid receptor antagonist, and naltriben, a selective delta 2-opioid receptor antagonist, on the capsaicin-induced cough reflex were studied in mice. I.p. administration of BNTX in doses from 0.1 to 3.0 mg/kg reduced the number of coughs dose dependently. The antitussive effect of BNTX was antagonized by [D-Pen2,5]enkephalin (DPDPE), a selective delta 1-opioid receptor agonist, while [D-Ala2]deltorphin II, a selective delta 2-opioid receptor agonist, had no effect on the antitussive effect of BNTX. Pretreatment with nor-binaltorphimine, a selective kappa-opioid receptor antagonist, had no significant effect on the antitussive effect of BNTX. I.p. administration of naltriben, in doses of 1 and 3 mg/kg, also significantly decreased the number of coughs. Although the antitussive effect of naltriben was antagonized by nor-binaltorphimine, the antitussive effect of naltriben was not attenuated by either DPDPE or [D-Ala2]deltorphin II. The antitussive effects of neither BNTX nor naltriben were antagonized by beta-funaltrexamine, a selective mu-opioid receptor antagonist. Thus, it seems likely that the delta 1-opioid receptor antagonism may be involved in the antitussive effect of delta-opioid receptor antagonists.

Animals↗
PubMed1994

Antinociceptive effect of lipopolysaccharide from Pantoea agglomerans on streptozotocin-induced diabetic mice.

The antinociceptive effect of lipopolysaccharide from Pantoea agglomerans (LPSp) in streptozotocin-induced diabetic mice was examined. Although subcutaneous (s.c.) administration of LPSp produced a dose-dependent inhibition of the tail-flick response in both non-diabetic and diabetic mice, the antinociceptive response was greater in diabetic mice than in non-diabetic mice. The antinociceptive effects of LPSp in both diabetic and non-diabetic mice were significantly antagonized by s.c. administration of naltrindole, a selective delta-opioid receptor antagonist or nor-binaltorphimine, a selective kappa-opioid receptor antagonist, but not by beta-funaltrexamine, a selective mu-opioid receptor antagonist. These results suggest that LPSp produces a marked antinociceptive effect in diabetic mice through the activation of delta- and kappa-opioid receptors.

Analgesics↗
PubMed1994

Streptozotocin-induced diabetes selectively reduces antinociception mediated by mu 1-opioid receptors, but not that mediated by mu 2-opioid receptors.

We assessed the effect of naloxonazine, a selective mu 1-opioid receptor antagonist, on antinociception produced by intrathecal or intracerebroventricular injections of morphine in streptozotocin-induced diabetic mice. The antinociceptive effect of morphine (10 micrograms), administered i.c.v., was significantly less in diabetic mice than in non-diabetic mice. The antinociceptive effect of i.c.v. morphine was significantly reduced in both diabetic and non-diabetic mice following pretreatment with naloxonazine. There were no significant differences in the antinociceptive effect of morphine (1 microgram, i.t.) in diabetic and non-diabetic mice. Furthermore, naloxonazine had no significant effect on the antinociceptive effect of i.t. morphine in either diabetic or non-diabetic mice. On the other hand, the antinociceptive effects of i.c.v. and i.t. morphine were significantly reduced following pretreatment with beta-funaltrexamine, a selective mu-opioid receptor antagonist, in both diabetic and non-diabetic mice. In conclusion, mice with diabetes are selectively hyporesponsive to supraspinal mu 1-opioid receptor-mediated antinociception, but are normally responsive to activation of spinal mu 2-opioid receptors.

Analgesics↗
PubMed1994

Reduction in ATP-sensitive potassium channel-mediated antinociception in diabetic mice.

To test our hypothesis that the abnormally low efficacy of mu-opioid agonists in diabetic mice may be due to functional changes in ATP-sensitive potassium channels, we evaluated the effects of cromakalim on the tail-flick latencies in diabetic and non-diabetic mice. Anti nociceptive effects of morphine (10 micrograms, ICV) in diabetic mice were significantly less than that in non-diabetic mice. Morphine-induced antinociception in non-diabetic mice was antagonized by pretreatment with glibenclamide (30 micrograms, ICV), an ATP-sensitive potassium channel blocker. Cromakalim (0.3 and 1 micrograms, ICV) produced significant, dose-dependent antinociception in non-diabetic mice, which was significantly reduced by pretreatment with glibenclamide. However, cromakalim did not markedly affect the tail-flick latencies in diabetic mice, even at higher doses (3 micrograms, ICV). On the other hand, [D-Pen2,5]enkephaline (DPDPE, 5 micrograms, ICV), a selective delta-opioid receptor agonist, produced significant antinociception in both diabetic and non-diabetic mice. Since pretreatment with glibenclamide significantly reduced the antinociceptive effect of DPDPE in non-diabetic mice but not in diabetic mice, delta-opioid receptor-mediated antinociception in diabetic mice may be independent of potassium channels. These results suggest that dysfunction of ATP-sensitive potassium channels may contribute to the demonstrated poor antinociceptive response of diabetic mice to mu-opioid agonists.

Adenosine Triphosphate↗
PubMed1994

Involvement of adenosine A1 receptors in antitussive effect in mice.

The effects of N6-cyclohexyladenosine, a selective adenosine A1 receptor agonist, on the capsaicin-induced cough reflex in mice were examined. I.c.v. administration of N6-cyclohexyladenosine in doses that ranged from 0.03 to 0.3 nmol decreased the number of coughs in a dose-dependent manner. Pretreatment with 8-cyclopentyl-1,3-theophylline, a selective adenosine A1 receptor antagonist, significantly reduced the antitussive effect of N6-cyclohexyladenosine. On the other hand, CGS21680 (0.3 and 1 nmol, i.c.v.), a selective adenosine A2 receptor agonist, had no significant effect on the number of capsaicin-induced coughs. These data suggest that adenosine A1 agonists may have a marked antitussive effect in mice.

Adenosine↗