Involvement of NMDA receptors and nitric oxide in the thermoregulatory effect of morphine in mice.

Morphine has long been known to have potent effects on body temperature. It has been suggested that both N-methyl-D-aspartate (NMDA) receptors and nitric oxide (NO) pathway are involved in thermoregulation and also known to play important roles in some of morphine effects. The aim of this study was therefore to investigate the contribution of NMDA receptors and NO to the thermoregulatory effect of morphine. Morphine produced a hypothermic effect, especially at the dose of 10mg/kg. Ketamine (5-40mg/kg, i.p.) and N(G)-nitro-L-arginine-methyl ester (L-NAME, 1-100mg/kg, i.p.) also produced hypothermic effects with their higher doses. At doses which themselves produced no effect on colonic temperature in mice, both ketamine (10mg/kg, i.p.) and L-NAME (10mg/kg, i.p.) enhanced the hypothermic effect of morphine (10mg/kg, i.p.). These results further support the relationship between NO and NMDA receptors and suggest a possible role of NMDA-NO pathway in the thermoregulatory effect of morphine.

Compound 48/80, a histamine-depleting agent, blocks the protective effect of morphine against electroconvulsive shock in mice.

We have shown that morphine has an anticonvulsive effect against maximal electroconvulsive shock (MES) in mice, and this effect is antagonized by histamine H1-receptor antagonists. Brain histamine is localized both in neurons and in mast cells, and morphine is known to enhance the turnover of neuronal histamine and to release histamine from mast cells. In the present experiments, compound 48/80 was injected chronically (0.5 mg/kg on day 1, 1 mg/kg on day 2, 2 mg/kg on day 3, 3 mg/kg on day 4, and 4 mg/kg on day 5, twice daily, ip) to deplete mast cell contents. Morphine (0.001-10 mg/kg, ip; N = 20) produced a dose-dependent anticonvulsive effect against MES seizure in mice with non-depleted mast cells, whereas it did not exert any anticonvulsive effect in mice with depleted mast cells. These results indicate that morphine produces its anticonvulsive effect against maximal electroconvulsive shock in mice by liberating histamine from mast cells.

Comparison of the effects of tenoxicam and mid-laser irradiation on chronic adjuvant arthritis in rats.

OBJECTIVE: This controlled experimental study was designed to compare the effects of a well-known NSAID, tenoxicam, with mid-laser irradiation on the inflammatory component of adjuvant-induced arthritis (AIA). Four groups of animals, each consisting of 10 Wistar rats, were included in the study. The primary concern was not to investigate the antiinflammatory effects of tenoxicam, but to compare the previously proven effects of this drug with a physical therapy agent which might be considered to have fewer side effects and/or contraindications. METHOD: The first group received only 0.1 ml of complete Freund's adjuvant (CFA) and served as the control for the other groups. The 2nd, 3rd and 4th groups, after having CFA injected into the plantar surfaces of their right paws, were treated with tenoxicam alone, mid-laser alone, or with a combination of the two, respectively. RESULTS AND CONCLUSION: All 3 groups showed significantly reduced paw edema compared with the control group. Although the reduction in paw edema in the animals treated with tenoxicam or with tenoxicam+ mid-laser was more significant, mid-laser is proposed as an alternative therapy for symptomatic relief in certain conditions well known to limit the use of NSAIDs.

The role of histamine H1 receptors in the thermoregulatory effect of morphine in mice.

Morphine is known to release histamine from mast cells and increase the turnover of neuronal histamine. It is also known that histamine receptors mediate some of the morphine effects. The contribution of histamine H1 and H2 receptors to the thermoregulatory effect of morphine in mice was investigated in the present experiments. Morphine produced a hypothermic effect, especially at the dose of 10 mg/kg. Although the histamine H1 receptor antagonist, dimethindene (0.1 mg/kg, i.p.), attenuated the hypothermic effect of morphine (10 mg/kg), a histamine H2 receptor antagonist, ranitidine (100 mg/kg, i.p.), had no effect. These results suggest that the hypothermic effect of morphine in mice is mediated, at least partly, through histamine H1 receptors.

The role of histamine H1-receptors in the anticonvulsive effect of morphine against maximal electroconvulsive shock in mice.

Morphine is known to release histamine from mast cells. It is also known that histamine receptors mediate some of morphine's effects on the central nervous system. The contribution of H1- and H2-receptors to the effect of morphine on maximal electroconvulsive shock in mice was investigated in the present experiments. Morphine showed a dose-dependent anticonvulsive effect, but produced spontaneous clonic convulsions at higher doses (100 mg/kg, i.p.). The anticonvulsive effect of morphine (1 mg/kg, i.p.) was antagonized by histamine H1-receptor antagonists, dimethindene (0.1 mg/kg, i.p.) promethazine (0.4 mg/kg, i.p.) and pheniramine (30 mg/kg, i.p.), and naloxone (10 mg/kg, i.p.), but not by the H2-receptor antagonist ranitidine (10-50 micrograms, i.c.v.). These results show that morphine has an anticonvulsive effect via histamine H1-receptors against maximal electroconvulsive shock in mice.

The role of H1- and H2-receptors in the effect of compound 48/80 in the asphyxiation and body temperature of mice.

Contribution of histamine H1- and H2-receptors to the effect of compound 48/80, a potent histamine releaser, upon asphyxiation and body temperature in mice was investigated in the present experiments. Compound 48/80 showed an apparent protective potency against hypoxia and significantly prolonged the latencies for convulsions and death in a dose-dependent manner. Compound 48/80 also decreased the body temperature, which was in relation with the antihypoxic effect. Both the H1-receptor antagonist, dimethindene, and the H2-receptor antagonist, ranitidine, attenuated the hypothermic effect of compound 48/80, indicating the involvement of central histamine through both the H1- and H2-receptors. Ranitidine had no effect on the protective effect of compound 48/80 against hypoxia-induced lethality, whereas dimethindene completely antagonized it. These results suggest that the protective effect of compound 48/80 against hypoxia is mediated through histamine H1-receptors and is not related to its ability to induce hypothermia.

The protective effect of moclobemide against hypoxia-induced lethality in mice is not due to a decrease in body temperature.

The protective effect of moclobemide, a reversible and highly selective inhibitor of monoamine oxidase-A, against hypoxia-induced lethality was investigated in the present experiment. Moclobemide showed an apparent protective potency against hypoxia and significantly prolonged the latencies for convulsions and death in a dose-dependent manner. Hypothermia is known to protect animals from hypoxia. Moclobemide also decreased body temperature in mice; however, the hypothermic effect was unrelated to the antihypoxic effect. These results suggest that the protective effect of moclobemide in hypoxia is not due to a decrease in body temperature.

Differential role of nucleus accumbens and caudate-putamen in mediating the effect of nomifensine and methamphetamine on ambulation and rearing of rats in the open-field test.

The effects of nomifensine (NOM) and methamphetamine (MA) on ambulation and rearing of rats in the open-field test were investigated. NOM and MA were injected i.p. into intact rats and nucleus accumbens (ACC)- and caudate-putamen (CP)-lesioned rats and infused into the ACC and CP. NOM (1-10 mg/kg, i.p.) and MA (1-5 mg/kg, i.p.) produced hyperactivity. However, NOM at 20 mg/kg, i.p. decreased the activity and induced repetitive head bobbing and squatting. Lesions of the ACC and CP increased open-field activity. However, lesion of the CP increased rearing more than lesion of the ACC. The increase in ambulation induced by NOM was inhibited by lesion of the ACC, whereas that induced by MA was inhibited by lesion of the CP. Although NOM (1-10 micrograms/2 microliters) and MA (0.5-10 micrograms/2 microliters) injections into the ACC and CP induced hyperactivity, the effect of NOM was greater after injection into the ACC, whereas the effect of MA was greater following injection into the CP. These results suggest that the ACC has a greater role in ambulation, while CP has a greater one in rearing. The present results, while they verified the significance of the ACC and CP in NOM- and MA-hyperactivity, also revealed a differential role of the ACC in NOM-hyperactivity and the CP in MA-hyperactivity.