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T Nabeshima

Publications and source records attributed to T Nabeshima.

At least 397 records · Page 22Linked to original sources
PubMed1983

Effects of opiate agonists on the conditioned suppression in motility of mice.

Mice exhibited a marked suppression in motility (conditioned suppression) when placed in the same environment in which they had previously received an electric footshock. The present study was designed to investigate the effects of opiate agonists on the conditioned suppression in motility. Morphine partially reduced the conditioned suppression in motility while cyclazocine attenuated it in a dose-dependent manner. On the other hand, ethylketocyclazocine and methionine-enkephalin had no effect. These results suggest that sigma receptor may be more important than mu receptor for opiate-induced attenuation of the conditioned suppression in motility of mice.

Animals↗
PubMed1983

Contribution of different opioid systems to footshock-induced analgesia and motor suppression.

Mice, subjected footshock, showed a significant increase of pain threshold and motor suppression immediately after the footshock and both effects were partially antagonized by pretreatment with naloxone at high doses. The magnitude of footshock-induced analgesia, but not motor suppression, was significantly less in morphine-tolerant mice than in non-tolerant mice. On the other hand, the magnitude of motor suppression, but not analgesia, was significantly less in ethylketocyclazocine- and pentazocine-tolerant mice than in non-tolerant mice. Furthermore, the apparent development of tolerance to both phenomena by successive daily footshocks was strikingly different. Tolerance to footshock-induced analgesia was induced on day 4 by the successive footshocks, while tolerance to motor suppression was not observed until day 17 of successive daily footshocks. In addition, the antinociceptive effect of morphine was significantly attenuated in mice tolerant to footshock-induced analgesia. These results suggest that different opioid systems may participate in footshock-induced analgesia and motor suppression. In addition, it is suggested that footshock-induced analgesia may be mediated by mu and/or delta receptors and motor suppression may be mediated by kappa and/or delta receptors.

Analgesics, Opioid↗
PubMed1983

Effect of lesions in the striatum, nucleus accumbens and medial raphe on phencyclidine-induced stereotyped behaviors and hyperactivity in rats.

The effect of lesioning the striatum, nucleus accumbens and medial raphe on phencyclidine(PCP)-induced stereotyped behaviors and hyperactivity was investigated to determine the site or sites of actions of PCP in rats. Bilateral lesions of the striatum diminished or abolished all the parameters of PCP-induced stereotyped behaviors, including sniffing, back pedalling, turning and head weaving 7 days after the operation. The medial raphe lesion significantly reduced PCP-induced back pedalling and head weaving. Bilateral lesions of the ventral portion of the nucleus accumbens did not affect the PCP-induced stereotyped behaviors. On the contrary, none of the lesions altered the sensitivity to PCP-induced hyperactivity 7 days after the operation. These results suggest that PCP-induced stereotyped behaviors may be mediated in the striatum and the medial raphe but not the nucleus accumbens. Furthermore, PCP-induced hyperactivity may not result from PCP effects on these discrete brain areas.

Animals↗
PubMed1983

Chronic phencyclidine increases methionine-enkephalin level in mouse striatum.

The chronic administration of phencyclidine-HCl (PCP-HCl), 10 mg/kg, for 6-7 days resulted in a significant increase in the striatal methionine-enkephalin level, although acute administration induced no change of methionine-enkephalin level in this area. The methionine-enkephalin levels in other areas investigated, i.e. the medulla oblongata/pons, the midbrain, the hypothalamus and the cortex, were unchanged after chronic PCP treatment. These results suggest that chronic administration of PCP alters the enkephalinergic neuronal activity in the striatum.

Animals↗
PubMed1983

Diisopropylfluorophosphate and GABA synaptic function: effect on levels, enzymes, release and uptake in the rat striatum.

The present study revealed that diisopropylfluorophosphate increased the GABA and glutamate levels, decreased the uptake of GABA, decreased the spontaneous release of GABA and did not exhibit its effects on the metabolic enzymes of GABA, glutamic acid decarboxylase and GABA-transaminase. These results, together with our previous finding that the postsynaptic GABA receptor population is increased by DFP treatment, indicate that GABA transmission is affected by DFP. An overall enhancement of GABA function appears to be involved in DFP poisoning; it is suggested that this may be a compensatory mechanism to counteract the cholinergic hyperactivity.

4-Aminobutyrate Transaminase↗
PubMed1983

[Pharmacological actions of eptazocine (l-1,4-dimethyl-10-hydroxy-2,3,4,5,6,7-hexahydro-1,6-methano-1,H-4-benzazonine). 4. Antagonistic action of naloxone on eptazocine analgesia].

It was investigated whether the analgesic effects of eptazocine were antagonized by treatment with naloxone, one of the opiate antagonists, and whether morphine-induced effects were affected by eptazocine. The analgesic effects of eptazocine, similar to those of morphine, were completely antagonized by treatment with 0.5 mg/kg naloxone, s.c., as determined by the hot plate and pressure methods in mice and by the tail-flick method in rats. In contrast, as tested by the acetic acid-induced writhing method in mice, the analgesic effect of eptazocine, similar to that of pentazocine, was not antagonized by treatment with 1.0 mg/kg naloxone, s.c., while that of morphine was antagonized by 0.5 mg/kg naloxone, s.c. Using the acetic acid-induced writhing method in mice, the pA2 values of naloxone were found to be the following order: eptazocine less than pentazocine less than morphine. In addition, the analgesic effect of morphine was dose-dependently antagonized by the treatment with eptazocine as determined by the pressure method. Furthermore, the stimulating effect of morphine on spontaneous locomotor activity was also antagonized by eptazocine. These results suggest that eptazocine may be classified as one of the opiate agonist-antagonists.

Analgesics↗
PubMed1983

Effect of morphine on the responses to and disposition of phencyclidine in mice. I. Enhancement of phencyclidine effects by acute morphine administration.

Morphine elicited a dose-related increase in the duration of phencyclidine (PCP)-induced motor incoordination. In the open field behavioral observations, morphine enhanced the PCP-induced decrease in the number of ambulation and rearing. Morphine potentiated the PCP-induced decrease in body temperature. The LD50 of PCP was significantly decreased in the presence of morphine. An opiate antagonist, naloxone, antagonized the morphine-induced effects without influencing the pharmacological actions of PCP itself. The levels of hepatic microsomal cytochrome P-450 and cytochrome b5 and the activities of NADPH dehydrogenase and NADPH cytochrome c reductase were unaffected by morphine treatment. The half-lives of PCP in serum and brain were increased by the concurrent administration of morphine. The ratio of the liver weight to body weight and aniline hydroxylase activity in hepatic microsomal fraction were decreased in the morphine-treated group compared with the control group; this is indicative of a possible reduction in the oxidative metabolism of PCP. The results indicate that acute administration of morphine enhances a variety of pharmacological effects of PCP; an inhibition of PCP disposition by morphine may be a mechanism involved in this process.

Aniline Compounds↗
PubMed1982

Phencyclidine-induced decrease of methionine-enkephalin levels in mouse brain.

The effects of acute administration of phencyclidine (PCP) on the steady state levels of methionine-enkephalin in discrete brain areas were investigated in mice. The methionine-enkephalin levels in the medulla oblongata-pons and the midbrain were decreased by the administration of PCP. However, PCP induced no change of the methionine-enkephalin levels in other brain areas at the dose range of 5-20 mg/kg. These results suggest that the pharmacological effects of PCP may involve changes in enkephalinergic neuronal activity.

Animals↗
PubMed1982

Acute and chronic effects of pentobarbital in relation to postsynaptic GABA receptors: a study with muscimol.

Muscimol, a GABA agonist, enhanced pentobarbital sleeping time in a dose-dependent manner. The GABA antagonists such as bicuculline and picrotoxin, and the CNS stimulant such as pentylenetetrazol, inhibited pentobarbital sleeping time; however, all except picrotoxin produced less than 35% maximum inhibition. Picrotoxin, and agent which blocks the chloride ionophore of GABA-receptor complex, exhibited a parallel dose-response curve with respect to muscimol. Chronic administration of pentobarbital by pellet implantation induced tolerance as evidenced by decreased sleeping time; the tolerance receded gradually upon abrupt withdrawal. Muscimol enhanced pentobarbital sleeping time both in tolerant and withdrawal mice. Na+-independent GABA-receptor binding, using [3H]muscimol as a ligand, was increased after acute and chronic pentobarbital administration; withdrawal of the pentobarbital reversed the increase in receptor population. None of the treatments altered the affinity of [3H]muscimol binding. These results support the contention that pentobarbital (a) directly acts on the postsynaptic chloride ionophore and (b) augments GABA-mediated postsynaptic effects. The functional significance of the increase in GABA receptor population after pentobarbital treatment is unclear.

Animals↗
PubMed1982

Development of dispositional tolerance to phencyclidine by osmotic minipump in the mouse.

Development of tolerance to phencyclidine (PCP) was assessed in male ICR mice, using motor incoordination as a parameter. The implantation of a PCP (1-3 mg/day/mouse for 1-5 days)-containing osmotic minipump, induced tolerance, as evidenced by a gradual reduction of the duration of motor incoordination. The degree of tolerance exhibited dose and time dependency. Even after the removal of the PCP pump (1 mg/day/mouse for 5 days), the tolerance remained to the same degree for at least 4 days. The hepatic microsomal cytochrome P-450, cytochrome b5 and nicotinamide adenine dinucleotide phosphatase (NADPH)-cytochrome c reductase activities were found to be elevated in tolerant mice (2 mg/day/mouse for 5 days). The half-life of PCP in the brains of tolerant mice was likewise decreased. These data indicate a dispositional tolerance for PCP. It appears that the administration of PCP by the osmotic minipump offers a convenient method for inducing PCP tolerance.

Animals↗
PubMed1982

Alterations of synaptic high and low affinity opiate binding sites after acute and chronic morphine administration in mice.

1. The opiate receptor binding to whole brain synaptic membranes obtained from mice subjected to acute and chronic morphine administration and precipitated withdrawal was investigated. 2. The number of high and low affinity binding sites was significantly higher in morphine tolerant group than in control; acute administration of morphine also induced an increase in the number of binding sites, though this increase was significantly lower as compared to tolerant group. 3. The affinity of both high and low affinity sites, however remained unchanged after acute or chronic treatment. In contrast, both the affinity and the number of binding sites were significantly reduced after precipitated withdrawal, compared to the tolerant group. 4. Sodium chloride enhanced the antagonist binding and inhibited the agonist binding in both tolerant and non-tolerant groups. 5. It is concluded that (a) the increase in the number of receptors during tolerance development is an extension of the acute effect of morphine, (b) the character of tolerant membrane is qualitatively same as that of non-tolerant membrane, (c) upon withdrawal, the receptor population is brought back to normal; the altered higher, affinity after withdrawal may be a compensatory effect as a corollary to the withdrawal-induced decrease in receptor population.

Animals↗
PubMed1982

An analysis of GABA receptor changes in the discrete regions of mouse brain after acute and chronic treatments with morphine.

The effects of morphine on the affinity and distribution of GABA receptors in the mouse regions (striatum, medulla, diencephalon, cortex, and cerebellum) were investigated in relation to: (a) acute administration, (b) chronic administration (tolerance), (c) precipitated withdrawal by naloxone, an opiate antagonist, and (d) abrupt withdrawal for 8 and 24 h. The alterations in the affinity as reflected by the dissociation constant (KD) and the number of receptors (Bmax) in the synaptic membranes obtained from controls and various treatments were determined by radioligand binding assay using [3H]muscimol as a ligand. Significant changes were observed in striatum, medulla, and diencephalon, whereas other regions including whole brain exhibited marginal changes. In general the number of GABA receptors increased after tolerance development, which upon abrupt withdrawal returned to control levels except in the case of naloxone-induced precipitated withdrawal. The affinity changes in different regions were diverse in nature and were not evident in the whole brain membranes. These results indicate that: (as) the regional alterations in the affinity and distribution of GABA receptors may play a role in the induction, maintenance, and regression of morphine tolerance; (b) abrupt withdrawal and antagonist precipitated withdrawal affect the GABA system differently, (c) chronic morphine treatment appears to influence the GABA receptors in the cerebellum, a region generally known for its lack of opiate receptors.

Animals↗
PubMed1982

[Detection of auditory impairment in the offsprings caused by drug treatment of the dams].

To study the auditory impairment induced by prenatal administration of aminoglycosides in the offspring, the shuttle box method to measure the auditory threshold of rats (Kameyama et al., Folia pharmacol. japon. 77, 15, 1981) was employed. Four groups of pregnant rats were administered 200 mg/kg kanamycin sulfate (KM), 200 mg/kg dihydrostreptomycin sulfate (DHSM), 100 mg/kg neomycin sulfate (NM), or 1 ml/kg saline intramuscularly from the 10th to the 19th day of pregnancy. The auditory threshold of the offspring could be measured by the shuttle box method in about 90% of the live born rats at the age of 100 days. The auditory thresholds of the groups were as follows (mean +/- S.E.): saline group, 53.8 +/- 0.6 dB (N = 36); KM group, 63.8 +/- 1.1 dB (N = 34); DHSM group, 60.0 +/- 1.2 dB (N = 29); NM group, 62.4 +/- 1.2 dB (N = 24). Auditory thresholds of drug-treated groups were significantly higher than that of the saline group. However, no increase in the auditory threshold of the mother rat was detected after treatment with aminoglycosides. In addition, the experimental procedure of the shuttle box method is very easy, and the auditory threshold of a large number of rats could be measured in a short period. These findings suggest that this method is a very useful one for screening for auditory impairment induced by prenatal drug treatment in rat offspring.

Aminoglycosides↗
PubMed1982

Effects of oral administration of chlordecone and mirex on brain biogenic amines in mice.

Levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and the 5-HT metabolite, 5-hydroxyindole acetic acid (5-HIAA) were determined in brains of mice after daily oral administration of 10, 25 or 50 mg/kg of chlordecone or mirex until mortality occurred. Significant decreases in whole brain and striatal DA levels were observed in chlordecone-treated mice exhibiting tremors. Mirex had no effect at the 3 doses tested. In mice treated with chlordecone or mirex, the 5-HT levels were elevated only in animals exhibiting severe tremors or diarrhea, respectively. NE levels were not altered by chlordecone or mirex. These results suggest that chlordecone-induced neurotoxicity may be due in part to a decrease in the inhibitory state of dopamine neurons.

Administration, Oral↗
PubMed1982

Determination of methionine-enkephalin, norepinephrine, dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylacetic acid (HVA) in brain by high-pressure liquid chromatography with electrochemical detector.

High-pressure liquid chromatography with electrochemical detection is utilized in a procedure for the determination of methionine-enkephalin (MET-ENK), norepinephrine (NE), dopamine (DA), 3, 4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylacetic acid (HVA) in same brain tissue samples. The high degree of selectivity and sensitivity (picomole limits for each component) makes this technique directly applicable to extremely small samples. After optimal conditions had been established, the procedure was employed in the determination of MET-ENK, NE, DA, DOPAC and HVA contents in whole brains, 7 discrete brain areas of mice and rats.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

Responses of the pituitary-adrenal system of mice to an environment of high temperature and humidity.

1. Changes in plasma glucose and corticosterone levels under an environment of high temperature and humidity similar to summers in Japan were investigated. 2. When mice were exposed to high temperature (30-40 degrees C) and humidity (70%), the plasma glucose levels increased with a short-term exposure and decreased with a long-term exposure compared to that of the control mice housed at room temperature (23 degrees C) and humidity (55%). 3. The magnitude of increase of plasma corticosterone levels depended on the degree of ambient temperature and the duration of exposure to the stressful conditions. The plasma corticosterone concentration was highest at 2 hr after initiation of the temperature stress and was reduced at 4 and 6 hr after the treatment: The plasma corticosterone had returned to the control level at 8 hr after the exposure. 4. The dexamethasone treatment inhibited the increase of plasma corticosterone in stress-mice. 5. These results suggest that the response of the plasma corticosterone is a better index than that of glucose for estimation of stress-degree.

Animals↗