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Biomedical subjects

T Nabeshima

Publications and source records attributed to T Nabeshima.

At least 361 records · Page 20Linked to original sources
PubMed1986

Comparison of tizanidine and morphine with regard to tolerance-developing ability to antinociceptive action.

The antinociceptive, tolerance-developing and anti-withdrawal activities of tizanidine [5-chloro-4-(2-imidazolin-2-yl-amino)-2,1,3-benzo-thiadiazole] were investigated by comparing its effects with those of morphine and clonidine in tail-flick-, hot plate-, acetic acid-induced writhing-, and naloxone-precipitated withdrawal jumping-tests. The antinociceptive action of tizanidine was not altered by naloxone, while that of morphine was antagonized. Tolerance to the tizanidine-induced antinociceptive action and to motor incoordination was developed by successive administration of tizanidine. In the tizanidine-tolerant mice, the antinociceptive action of morphine was significantly decreased, but not sleeping time induced by pentobarbital. The action of tizanidine was not modified in the morphine-tolerant mice. Tizanidine failed to induce morphine-withdrawal jumping and to inhibit naloxone-precipitated withdrawal jumping in the morphine-dependent mice. Cross tolerance to the antinociceptive action induced by tizanidine and clonidine was developed. These results suggest that alpha 2-adrenoreceptors may be involved in the action mechanism of tizanidine, but not opioid receptors. Functional tolerance to tizanidine action may be developed by successive administration of tizanidine.

Analgesics↗
PubMed1986

Phencyclidine-induced stereotyped behaviors after injection of morphine and N-allylnormetazocine (SKF 10,047) in rats.

We investigated the effects of N-allylnormetazocine (SKF 10,047) and morphine on the stereotyped behaviors induced by the intraperitoneal injection of phencyclidine (PCP). PCP-induced turning and backpedalling were significantly potentiated by pretreatment with SKF 10,047 (10 mg/kg) but sniffing and head weaving were not. On the other hand, pretreatment with morphine dose-dependently attenuated PCP-induced sniffing and head weaving, but not turning and backpedalling. These results suggest that PCP-induced stereotypy may be mediated by not only a sigma opioid receptor but also some other receptors. In addition, each component of PCP-induced stereotypy may be controlled by different opioid systems and/or neuronal systems.

Animals↗
PubMed1986

Step-down-type passive avoidance- and escape-learning method. Suitability for experimental amnesia models.

A method for evaluating passive avoidance- and escape-learning responses simultaneously has been developed for the study of learning and memory in mice. Prolongation of the step-down latency and shortening of the escape latency in the retention test depended on the strength of the voltage of the electric shocks delivered during the training test. Therefore, the step-down latency and escape latency may be good parameters of learning and memory performance. By cycloheximide treatment immediately after training, the step-down latency and escape latency were shortened and prolonged, respectively, in a dose-related manner, and the relationship between the step-down latency and escape latency was significant. Treatment with cycloheximide within 30 min after training caused significant amnesia, but not after more than 60 min. Furthermore, amnesic action of cycloheximide developed 24 hr after the treatment, but not within 4 hr. On the other hand, the step-down latency and/or the escape latency in the training test were changed by pretreatment with diethyldithiocarbamate and scopolamine. Therefore, the amnesic action of these drugs administered before the training should be investigated in detail. The present method, simultaneously estimating passive avoidance- and escape-learning responses, may be useful for the development of experimental amnesia models.

Amnesia↗
PubMed1986

Involvement of opioid receptors in hypo- and hyperthermic effects induced by phencyclidine in mice.

Experiments were conducted in order to examine the mechanism of changes in body temperature induced by phencyclidine (PCP) in mice. It is well known that morphine changes body temperature in a biphasic manner. PCP also produced hyperthermia at low doses (5 and 10 mg/kg) and hypothermia at high dose (40 mg/kg). The changes in body temperature induced by PCP were blocked by naloxone, a mu antagonist. Pretreatment with morphine (2.5 mg/kg), a mu agonist, or ethylketocyclazocine (EKC: 2.5 mg/kg), a kappa agonist, potentiated hypothermia induced by high dose of PCP. Effects of morphine and EKC on PCP-induced hypothermia were antagonized by naloxone. N-Allylnormetazocine (SKF 10 047: 20 mg/kg), a kappa and mu antagonist, antagonized PCP- and EKC + PCP-induced hypothermia but not morphine + PCP-induced hypothermia. Furthermore, Mr 2266, a kappa antagonist, antagonized PCP (10mg/kg)-induced hyperthermia and EKC + PCP-induced hypothermia. It is suggested that PCP may affect thermoregulation through mu and/or kappa opioid receptor mechanisms.

Animals↗
PubMed1986

Conditioned suppression and opioid kappa receptor in mice.

Mice exhibited a marked suppression of motility (conditioned suppression) when placed in the same environment in which they had previously received an electric footshock. Furthermore, chronic morphine (mu agonist)-pretreated mice, as well as chronic vehicle-pretreated mice, exhibited the conditioned suppression but chronic ethylketocyclazocine (kappa agonist)- and pentazocine (kappa agonist)-pretreated mice did not. On the other hand, in the synaptic membranes of the chronic vehicle- and morphine-pretreated mice showing conditioned suppression, the specific binding of [3H]phencyclidine (sigma agonist) and [3H]naloxone (mu antagonist) significantly increased, while the specific binding of [3H]ethylketocyclazocine did not change compared to those of the corresponding control groups. However, in the chronic pentazocine- and ethylketocyclazocine-pretreated groups showing non-conditioned suppression, the specific binding of [3H]phencyclidine and [3H]naloxone were not altered. Moreover, a decrease of [3H]ethylketocyclazocine binding was observed in the chronic pentazocine-pretreated group. These results suggest that the binding function of different opioid receptor subtypes may be altered differently by stress, and that the kappa receptor may be important for the conditioned suppression of motility in mice.

Animals↗
PubMed1986

Role of dopaminergic and GABAergic mechanisms in discrete brain areas in phencyclidine-induced locomotor stimulation and turning behavior.

This study was designed to test whether phencyclidine (PCP)-induced turning behavior and locomotor stimulation result from the action of this drug on functionally different neuronal systems and different sites of the brain. PCP produced turning behavior towards the drug injection side with unilateral injection of PCP (50-100 micrograms) into the globus pallidus, but not the nucleus accumbens and the caudate nucleus. This turning behavior was strongly attenuated by a gamma-aminobutyric acid (GABA) antagonist, bicuculline, and by pimozide which reduces dopaminergic transmission in non-injection sites. Turning behavior induced by intraperitoneal injection of PCP (7.5 mg/kg) was enhanced by a GABA agonist, baclofen, and attenuated by GABA antagonists (bicuculline, picrotoxin). On the other hand, PCP produced significant locomotor stimulation, sniffing, rearing and forward locomotion with unilateral injection of 25-100 micrograms into the nucleus accumbens and the caudate nucleus. These behaviors were strongly antagonized by intraperitoneal injection of pimozide. The locomotor stimulation induced by intraperitoneal injection of PCP (5 mg/kg) was markedly enhanced by a small dose of methamphetamine and, by contrast, attenuated by reserpine, 6-hydroxydopamine, haloperidol, pimozide and a low dose of apomorphine which inhibits the release of dopamine by the stimulation of presynaptic receptors. These results suggest that PCP-induced turning behavior may be produced through stimulation of GABAergic transmission in the globus pallidus, although PCP-induced locomotor stimulation, sniffing, rearing and forward locomotion may be produced by increasing dopaminergic transmission in the nucleus accumbens and the caudate nucleus.

Animals↗
PubMed1986

Role of dopaminergic and serotonergic neuronal systems in the prefrontal cortex of rats in phencyclidine-induced behaviors.

This study was designed to determine the action sites of phencyclidine (PCP) involved in the development of behaviors such as head-weaving, immobility, turning and backpedalling in relation to dopaminergic and serotonergic neuronal functions. Injection of PCP into the caudate nucleus or prefrontal cortex dose-dependently produced head-weaving, although the injection of PCP into the nucleus accumbens failed to produce head-weaving. The intensity of head-weaving induced by injection of PCP into the prefrontal cortex was relatively high when compared to that induced by injection of PCP into the caudate nucleus or lateral ventricle. Pretreatment with p-chlorophenylalanine (300 mg/kg), a serotonin (5-HT) synthesis inhibitor, attenuated head-weaving induced by injection of PCP into the prefrontal cortex. Injection of PCP (50-100 micrograms) into the prefrontal cortex also produced immobility for 5 min post-injection. Rats pretreated with pimozide (1 mg/kg), a dopamine (DA) antagonist, also produced immobility after the injection of PCP into the prefrontal cortex and this effect was attenuated by pretreatment with ritanserin, a 5-HT2 receptor antagonist. On the other hand, pretreatment with methamphetamine attenuated PCP (5 and 7.5 mg/kg)-induced turning and backpedalling but not head-weaving. Pretreatment with large doses of apomorphine, a DA agonist, also greatly attenuated PCP (7.5 mg/kg)-induced behaviors, i.e. head-weaving, turning and backpedalling. These effects of DA agonists were prevented by haloperidol (0.25 mg/kg), a DA antagonist. These results suggest that PCP-induced turning and backpedalling may be mediated by reducing dopaminergic transmission, although PCP-induced head-weaving and immobility may be produced by increasing serotonergic transmission in the prefrontal cortex.

Animals↗
PubMed1986

[Pharmacological action of eptazocine (l-1,4-dimethyl-10-hydroxy-2,3,4,5,6,7-hexahydro-1,6-methano-1H-4-benz azonine). (V). A comparison of eptazocine, pentazocine and morphine with regard to ability of tolerance development after successive administration].

It was investigated whether tolerance to the pharmacological actions and cross-tolerance between eptazocine and pentazocine/morphine were developed by successive administration of eptazocine. In the experiments of mice, successive administration of eptazocine failed to decrease the pharmacological actions of eptazocine on the acetic acid-induced writhing, the pressure and the wheel cage methods. Cross-tolerance between eptazocine and pentazocine/morphine was not observed. Tolerance to the actions of pentazocine and morphine was developed on the wheel cage and the acetic acid-induced writhing/pressure methods, respectively. Cross-tolerance between pentazocine and morphine was also developed on the pressure method. On the tail flick method of rats, tolerance to the action of eptazocine was observed, similar to morphine, but not cross-tolerance between eptazocine and morphine. These results suggest that there is species difference between mice and rats with regard to the ability of tolerance development and that the mechanisms of tolerance development between eptazocine and pentazocine/morphine may be different since eptazocine failed to show cross tolerance to these analgesics.

Analgesics↗
PubMed1986

[A method for evaluating visual impairments using operant behavior in mice].

A behavioral method, using a shuttle box (one of the conditioned behaviors) for assessing visual function in mice, was investigated. Normal ICR mice were trained to avoid the unconditioned stimulus (electric footshock) during the presentation of conditioned stimuli (tone and light). After acquisition of avoidance response, normal ICR mice were presented randomly tone or light as the conditioned stimulus. The percent of avoidance in the presentation of light was decreased suddenly, but that of tone was not. However, the decrease of avoidance response to light stimulus was recovered by following trainings. The mice, which had acquired the condition response to tone and light stimulus alone, were treated in their cornea with 4N NaOH. The decrease of percent of avoidance in the mice with alkali-treated cornea after differentiation of conditioned stimuli did not recover following training. These results suggested that visual impairment of mice can be detected by this method. Therefore, we attempted to detect the visual impairments of dominant (Cts) and recessive (cac) hereditary cataract mice, hereditary retina degenerated mice (C3H) and first filial generation mice of C3H, F1 [(ICR X C3H) F1]. The acquisition curves of both Cts and cac cataract mice were similar to that of normal ICR mice, but those of C3H and F1 were similar to that of ICR mice treated with alkali. Moreover, changes in recovery %, which was calculated from avoidance response in the presentation of light alone after differentiation of conditioned stimuli, corresponded to the above results. These findings demonstrated that the visual impairment of Cts and cac cataract mice is weak, while that of C3H and F1 mice is strong.

Animals↗
PubMed1986

Potentiation of phencyclidine-induced dopamine-dependent behaviors in rats after pretreatments with serotonin-depletors.

This study was designed to assess whether phencyclidine (PCP) produces dopamine (DA)-dependent behaviors such as licking, gnawing and biting (which are not observed in normal rats) in rats after pretreatments with a tryptophan hydroxylase inhibitor, p-chlorophenylalanine (PCPA) and specific serotonergic neuronal toxin, p-chloroamphetamine (PCA). Apomorphine (APO, 0.5 mg/kg) and methamphetamine (MAP, 2.5 mg/kg) mainly induced DA-dependent behaviors, including rearing and sniffing with occasional licking, in the vehicle-pretreated rats. APO (0.5 mg/kg)-induced DA-dependent behaviors significantly increased in the PCA- and PCPA-pretreated rats, in which serotonergic activity was greatly depressed but dopaminergic activity was normal. MAP (2.5 mg/kg)-induced DA-dependent behaviors were also significantly increased in the PCA-pretreated rats but not PCPA-pretreated rats. On the other hand, at doses of 2.5-7.5 mg/kg, PCP mainly caused stereotyped behaviors such as head-weaving, backpedalling, turning and DA-dependent behavior, such as sniffing, in the vehicle-pretreated rats. The PCP-induced stereotyped behaviors were attenuated by pretreatment with PCA and PCPA. In contrast, PCP-induced DA-dependent behavior, sniffing, was converted into more intense behaviors such as licking, gnawing and biting by pretreatment with PCA. These effects of PCP were also observed in rats pretreated with PCPA, although the degree was less than that by pretreatment with PCA. These results may indicate that serotonergic neuronal systems inhibitory regulate dopaminergic systems in PCP-induced behavioral responses.

Animals↗
PubMed1986

Effect of tizanidine on body temperature in the mouse.

The effect of tizanidine [5-chloro-4-(2-imidazolin-2-yl-amino)-2,1, 3-benzothiadiazole] on core temperature in the mouse was investigated in comparison with that of clonidine. Tizanidine decreased core temperature in unanaesthetized, freely-moving normal mice. Clonidine produced hypothermia in normal mice. The alpha 2-antagonist yohimbine produced an antagonism to tizanidine- and clonidine-induced hypothermia, while naloxone failed to antagonize the hypothermia. It is concluded that tizanidine and clonidine produce a similar hypothermic effect via an alpha 2-adrenoreceptor, but not an endogenous opioid system.

Animals↗
PubMed1985

Conformational changes of opioid receptor induced by the electric footshock.

The present electric shock (ES) schedule followed in these experiments produced different functional changes in endogenous putative opioid agonist- and antagonist-type receptors, depending on the type of receptor: the amount of antagonist binding was increased by ES application, while the amount of agonist binding was decreased. In order to elucidate the mechanism of these changes, we investigated whether ES application was able to affect sulfhydryl-groups and phospholipids of endogenous opioid receptors. In comparison to the control membrane, the increased antagonist binding sites of the ES membrane were liable to be inactivated by the sulfhydryl-modifying reagents, N-ethylmaleimide (NEM) and iodoacetamide. However, in the presence of 100 mM Na, the antagonist binding sites of both the control and ES membranes were inactivated by NEM in the same manner. On the other hand, the agonist binding sites of both membranes were similarly inactivated by NEM regardless of the absence or presence of 100 mM Na. Another sulfhydryl-modifying reagent, such as p-chloromercuriphenylsulfonic acid, did not produce any difference between the control and ES membranes. The increased antagonist binding sites of the ES membrane were also liable to be inactivated by phospholipase A2. These results suggest that the present ES schedule followed in these experiments produces conformational changes in endogenous opioid receptors in the rat brain. As a result of these conformational changes, the amount of binding in the antagonist sites may be increased, while the amount of binding in the agonist sites may be decreased. However, the increased antagonist binding sites may be liable to be inactivated by NEM, iodoacetamide and phospholipase A2.

4-Chloromercuribenzenesulfonate↗
PubMed1985

Involvement of different opioid receptor subtypes in electric shock-induced analgesia and motor suppression in the rat.

We have investigated the correlation of electric shock-induced behavioral changes and functional alterations of endogenous opioid receptor subtypes. The degree of electric shock-induced behavioral changes, such as analgesia and motor suppression, was dependent on the duration of and time after electric shock application. The electric shock-induced behavioral changes were completely antagonized by naloxone. The apparent development of tolerance to both behavioral effects as a result of successive daily electric shock was different: Tolerance to electric shock-induced analgesia developed after 2 days' successive electric shock application, while tolerance to motor suppression was not observed even after 7 days' successive electric shock application. There was a decrease of [3H][D-Ala2, Met5]enkephalinamide ([3H]DAMEA, delta agonist) binding and an increase of [3H]naloxone (mu antagonist) binding when potent electric shock-induced analgesia developed. On the other hand, the binding of [3H]DAMEA and [3H]ethylketocyclazocine (kappa agonist) was significantly changed when locomotion was suppressed. These results suggest strongly that different opioid systems may participate in electric shock-induced analgesia and motor suppression: electric shock-induced analgesia and motor suppression may be mediated by mu/delta and kappa/delta receptors, respectively.

Animals↗
PubMed1985

Effects of acute and chronic administrations of phencyclidine on the levels of serotonin and 5-hydroxyindoleacetic acid in discrete brain areas of mouse.

The effects of phencyclidine (PCP) on the levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in discrete brain areas of mouse were investigated. Following a single administration, PCP significantly increased at 60 min the level of 5-HT but not 5-HIAA in the cortex. However, acute administration of PCP induced no changes of 5-HT and 5-HIAA levels in other brain areas investigated. On the other hand, chronic treatment of PCP produced a significant increase the striatal 5-HT and 5-HIAA levels by about 30% and 20%, respectively. These increased levels were gradually returned to the control levels, and there was no difference of these levels between the control group and the 48 hr withdrawal group. The changes of 5-HT level in the hypothalamus were similar to those in the striatum. These results suggest that the pharmacological actions of PCP and tolerance development to PCP may be related to the functional changes of serotonergic neuronal activity.

Animals↗
PubMed1985

Functional alteration of opioid receptor subtypes in the mice exhibited conditioned suppression in motility.

Mice exhibit a marked suppression of motility (conditioned suppression) when placed in the same environment in which they had previously received the electric footshock. The present study was designed to investigate the functional change of opioid receptor subtypes in the conditioned suppression group using an opioid binding assay technique. In the synaptic membrane of the conditioned suppression group, the binding capacities of [3H]naloxone at high and low affinity binding sites and of [3H]phencyclidine at high affinity binding site were significantly increased compared to those of the control group. On the other hand, the binding capacity of [3H]ethylketocyclazocine at both affinity binding sites in the conditioned suppression group was not changed. These results suggest that the binding function of different opioid receptor subtypes may be altered differently by stress.

Animals↗