Biomedical subjects

T Nabeshima

Publications and source records attributed to T Nabeshima.

At least 379 records · Page 21Linked to original sources

PubMed1985

Antinociceptive action of tizanidine in mice and rats.

The antinociceptive action of tizanidine [5-chloro-(2-imidazolin-2-yl-amino)-2,1,3-benzothiadiazole], a centrally acting muscle relaxant, was evaluated after subcutaneous or peroral administration in mice and rats. Tizanidine strongly inhibited the writhing response induced by acetic acid, phenyl-p-benzoquinone and acetylcholine in mice, and its potency was found to be greater than that of morphine. Tizanidine showed antinociceptive action like morphine not only in tail pressure and electrical stimulation tests in mice but also in tail-flick tests in mice and rats. The antinociceptive action of tizanidine was unaffected by pretreatment with naloxone. These findings suggest that tizanidine develops relatively strong antinociceptive action by a nonopioid mechanism.

Analgesics↗

PubMed1985

Effects of phencyclidine in combination with morphine on the levels of met-enkephalin, dopamine, DOPAC and HVA in discrete brain areas of mice.

The study investigated the interaction between phencyclidine (PCP) and morphine in affecting the levels of met-enkephalin, dopamine, DOPAC and HVA in mice. Morphine 5 mg/kg alone and PCP 10 mg/kg alone failed to change the levels of met-enkephalin in the midbrain and striatum. However, PCP in combination with morphine produced an increase in met-enkephalin levels and a decrease in HVA levels. In the midbrain, there was a direct relationship between the decrease in met-enkephalin levels and the increase in HVA levels. These results suggest that PCP may change the function in dopaminergic and enkephalinergic neuronal systems in the midbrain and/or striatum.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1985

Electric footshock-induced changes in behavior and opioid receptor function.

The present electric shock (ES) schedule produced significant behavioral changes, such as analgesia and motor suppression, and functional changes in binding capacities for opioid agonist and antagonist. In the naloxone (5 mg/kg, SC 15 min before ES application) pretreated rats, these behavioral and biochemical changes were blocked. In addition, when preincubation (37 degrees C, 30 min) was not carried out in the process of preparation of synaptic membrane, the ES-induced functional changes in hibh affinity binding sites were not observed. Moreover, the present data indicated that preincubation may produce the destruction of [3H]-D-ala2,L-met5-enkephalinamide ([3H]-DAMEA) specific binding sites with the forced dissociation of endogenous delta-type opioid peptides from delta opioid receptors. In addition, the significant decrease of [3H]-DAMEA specific binding in the ES membrane suggested that delta-type opioid peptides were released more than steady state level by ES application and bound to the delta opioid receptors. Therefore, these results suggest that ES-induced behavioral and biochemical changes were mediated by opioid peptides which were released by ES application. In addition, the ES-induced analgesia may be mediated by high affinity delta opioid receptor.

Analgesia↗

PubMed1985

Phencyclidine-induced dopamine-dependent behaviors in chronic haloperidol-treated rats.

This study was designed to assess whether phencyclidine (PCP) produces dopamine (DA)-dependent behaviors such as licking, biting and gnawing at low doses after withdrawal from chronic haloperidol (HAL) treatment in rats. Low doses of PCP (2.5 and 5 mg/kg) produced licking, gnawing, biting and self-biting in rats after withdrawal from chronic HAL treatment, which were not observed in the vehicle-pretreated rats given PCP at the same dose range. These behaviors were similar to DA-dependent behaviors produced by methamphetamine and apomorphine in rats after withdrawal from chronic HAL treatment. The PCP-induced behaviors were attenuated by acute pretreatment of DA antagonist, HAL (0.25 mg/kg, IP). Furthermore, at doses of 5 or 7.5 mg/kg, PCP-induced head weaving and backpedalling, which were mediated by both DA and serotonin (5-HT) neurons, significantly increased in rats after withdrawal from chronic HAL-treatment. These results suggest that dopaminergic systems play an important role for PCP-induced behavioral responses.

Animals↗

PubMed1985

Differences of alteration in opioid systems induced by conditioned suppression and electric footshock in mice.

The motility, pain-threshold and opioid receptor activities of the synaptic membrane in mice showing conditioned suppression of motility were compared with those in mice given only electric footshock. Electric footshock caused analgesia and a decrease in motility, both of which were partially reversed by administration of high doses of naloxone. In contrast, mice exhibited a marked suppression of motility (conditioned suppression) but not analgesia when placed in the same environment 24 hr after the electric footshock in which the animals received the electric footshock. In the electric footshock group, the [3H]-naloxone binding capacity at low affinity site was increased. These results suggest that the increase in [3H]-naloxone binding capacity may play an important role in the behavioral changes of electric footshock group, but not conditioned suppression group.

Animals↗

PubMed1985

[Measurement of an auditory impairment induced by aminoglycosides using a shuttle box method in newborn rats].

To investigate the auditory impairment induced by the administration of aminoglycosides in the newborn, the shuttle box method was employed to measure the auditory threshold of rats. Five groups of newborn rats were administered kanamycin sulfate, 250 and 500 mg/kg, streptomycin sulfate, 250 and 500 mg/kg, or 1 ml/kg saline, subcutaneously, from the 10th to the 15th day of birth. The auditory threshold of the control group could be measured by the shuttle box method at the age of 100 days. The auditory threshold of the control group was 52.1 +/- 1.0 dB (N = 14). The auditory thresholds of the animals treated with kanamycin 250 mg/kg and streptomycin 250 mg/kg groups were measured in only 1 (61.0 dB) and 4 (64.8 +/- 4.6 dB), respectively, since the auditory toxicity of these drugs in newborn rats was stronger than adult rats. Auditory threshold of the 250 mg/kg streptomycin group was significantly higher than that of the control group. The animals which could not be measured for the auditory threshold had the ability to acquire conditioned avoidance response when both conditioned stimuli (tone and light) were presented. However, after differentiation of the stimuli, the percent avoidance to tone in these animals was significantly decreased and did not recover by the following trainings, while the percent avoidance to light was similar to that before the differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

[Application of a shuttle avoidance response in rats to evaluate a drug-induced visual impairment].

In attempts to study drug-induced visual impairment, we measured the visual threshold in rats using the shuttle box method. Male Wistar rats were trained to avoid an electric shock during the presentation of conditioned stimuli (light and/or tone). The percent of avoidance was significantly decreased in rats suffering, from valinomycin-induced cataracts or alkaline-burn on the cornea when light alone was used as the conditioned stimulus. However, these rats could respond correctly to the conditioned stimulus of tone. On the other hand, rats whose eyes were impaired before conditioning could acquire the avoidance response to the presentation of both tone and light. However, when these conditioned stimuli were presented separately, the animals could not avoid the shock in the presentation of light. From these results, it appears that this method is easily applied, and the visual impairment of many rats can be detected over a short period. This approach may be a useful method for screening visual toxicity of drugs.

Animals↗

PubMed1985

[Application of a response duration schedule in rats to evaluate visual and/or auditory threshold].

Determination of visual and auditory thresholds was carried out under a response duration schedule of tone and/or light-dipper presentation. This schedule enabled an exact assessment of visual and auditory sensitivities, since the direction and distance from the rat to the sound or light sources were constant, and the rat could thus acquire the conditioned behavior in a short time. The rat has to put its nose into the hole and hold it there until a conditioned stimulus (tone and/or light) was presented. The animal could get water-reinforcement by taking its nose out from the hole during the period of conditioned stimulus. To determine the visual threshold, the intensity of light was reduced, from 100 Lx (starting point) by 10 Lx steps in each trial, until the subject made 10 non-response trials (i.e., no dipper approach within 1.0 sec after the light onset) among 10 trials. In terms of auditory threshold, the intensity of 3, 7 and 10 KHz pure tone was reduced, from 90 dB by 10 or 2 dB steps in each trial, until the subject made 10 non-response trials among 10 trials. The light or tone intensity that prolonged the response latency 2 times compared to normal rats was taken as the threshold. The visual sensitivity in the rats suffering from alkaline-burn on its corneas decreased about 14 Lx. The auditory thresholds in rats were 19.5 +/- 1.3, 37.5 +/- 1.8 and 54.6 +/- 1.3 dB at 10, 7 and 3 KHz, respectively. The auditory sensitivity in the rats with cotton-stuffed ears and pierced eardrums decreased about 6 and 12 dB, respectively.

Animals↗

PubMed1985

The interaction of eptazocine, a novel analgesic, with opioid receptors.

The profile of action of eptazocine, a novel analgesic, on opioid receptors was investigated. Eptazocine caused a concentration-dependent inhibition against the [3H]-naloxone [( 3H]-NLX) specific binding to rat brain synaptic membrane in the absence of sodium cation and GTP (IC50; 7.83 +/- 1.57 microM). The ratios of IC50 values between the absence to the presence of sodium cation alone or sodium cation and GTP were 3.89 and 4.35, respectively. In addition, eptazocine (10 microM) also produced the significant decrease of [3H]-NLX specific binding in the mouse brain synaptic membrane. Moreover, the same dose eptazocine significantly decreased the [3H]-ethylketocyclazocine [( 3H]EKC) specific binding, but not [3H]-phencyclidine [( 3H]-PCP). These results suggest that eptazocine interacts with opioid receptor, and is classified as one of the opiate agonist-antagonist analgesics.

Analgesics↗

PubMed1985

The prolonging effect of N,N'-diallylpentobarbital on the drug-induced sleep and motor incoordination.

N-Allyl substituted derivatives of pentobarbital were prepared, and their pharmacological activities (hypnotic activity and anticonvulsant activity against pentylenetetrazol (PTZ)-induced seizures) were investigated with single intraperitoneal (i.p.) injection using mice. N-Monoallylpentobarbital (MAPB) was found to possess hypnotic activity [HD50 = 77.5(64.3-93.4) mg/kg, i.p.] and anticonvulsant activity [PTZ-ED50 = 23.5(14.2-38.9)mg/kg, i.p.]. N,N'-Diallylpentobarbital (DAPB) was devoid of not only the hypnotic activity of parent compound but also the anticonvulsant activity. The interaction of these N-allyl derivatives with barbiturates (pentobarbital (PB), barbital (B), phenobarbital (PheB), amobarbital (AB) and thiopental (TP] or diazepam (DZ) was further studied to characterize as antagonist or agonist. MAPB and DAPB (5-160mg/kg, i.p.) showed potent prolonging effect on PB-induced sleeping time and time of their peak effect was observed. The prolonging effects of these allyl compounds on PB-induced sleep were dose-dependent. Both compounds (80mg/kg, i.p.) also prolonged sleeping time induced by PheB, AB and TP. Although DAPB showed prolonging effect on B-induced sleep at a time interval 1 min, the compound shortened the sleeping time at 15 and 60 min. DAPB (5, 10 and 80mg/kg, i.p.) enhanced the DZ-induced motor incoordination.

Animals↗

PubMed1984

Role of sex hormones in sex-dependent differences in phencyclidine-induced stereotyped behaviors in rats.

This study was designed to assess the contribution of male and female sex hormones to sex-dependent differences in phencyclidine (PCP)-induced stereotyped behaviors. Female rats appeared to be more sensitive to PCP than were male rats as evidenced by stereotyped behaviors. Chronic testosterone treatment and ovariectomy decreased the susceptibility to PCP but increased the efficiency of hepatic drug metabolizing systems in female rats. On the contrary, an increased sensitivity to PCP and a decreased efficiency of hepatic drug metabolizing systems in male rats resulted from chronic treatment with estradiol and castration. It appears from these results that the male and female sex hormones are responsible for sex-dependent differences in PCP-induced stereotyped behaviors by means of changes in the metabolism of PCP.

Anesthesia↗

PubMed1984

Attenuation of pharmacological effects and increased metabolism of phencyclidine in morphine tolerant mice.

Mice were used for a study of the interaction between morphine and phencyclidine (PCP) in relation to lethality, motor incoordination, locomotor activity and rearing, together with the half-life of PCP, following continuous administration of morphine by pellet (75 mg base) implantation for 72 h and after removal of the pellets for 6 and 24 h. PCP induced motor incoordination and suppressed locomotor activity and rearing; these effects were enhanced in morphine 'pellet-implanted' mice and were attenuated in morphine 'pellet-removed' groups. The enhancing effect of morphine on the PCP responses was attributable more to the presence of residual morphine than to the alterations in its disposition. The morphine-induced increase in locomotor activity and analgesia was attenuated in PCP (40 mg/kg per day i.p. for 5 days) tolerant mice. The rate of decay of PCP in serum and brain or morphine pellet-implanted animals was not different; however, in the 24 h 'pellet-removed' group, the rate of decay of PCP was increased. The results indicate that there is a two-way cross-tolerance development between PCP and morphine. The phenomenon appears to involve both dispositional and functional adaptation mechanisms.

Animals↗

PubMed1984

Different changes by acute electric footshock of opioid agonist and antagonist receptors in rat brain.

Electric shock (ES) produces an opiate-like analgesia and catalepsy in rats, which may be mediated by endogenous opioid systems. The present study was designed to investigate the alterations of endogenous opioid receptors by an intermittent ES application. In a case of opiate agonists, [3H]dihydromorphine and [3H]D-Ala-Met-enkephalinamide, the application of ES produced a decrease of [3H]ligands' binding capacity. On the contrary, the binding capacity of the opiate antagonist [3H]naloxone was increased by the ES application. These results suggest that endogenous putative opioid agonist- and antagonist-type receptors are differently regulated in vivo.

Animals↗

PubMed1984

Sex-dependent differences in the pharmacological actions and pharmacokinetics of phencyclidine in rats.

This study was designed to assess the sex differences in phencyclidine(PCP)-induced ambulatory activity in an open-field, stereotyped behaviors, motor incoordination, tremor, salivation, the regional and subcellular distributions of PCP in the brain and the half-life of PCP in the brain and plasma. Female rats appeared to be more sensitive to PCP as evidenced by hyperactivity, stereotyped behaviors, motor incoordination, tremor, salivation and ataxia. The concentrations of PCP in female rat brain were higher than in the male rats in some discrete brain areas and subcellular fractions. The half-life of PCP in the brain and plasma was longer in female rats than in male rats. The inverse relationship of pharmacological responses to PCP and biotransformation of PCP in both sexes of rats suggests that sex differences in pharmacological actions of PCP depend largely on differences in ability to biotransform the drug.

Animals↗

PubMed1984

Serotonergic involvement in phencyclidine-induced behaviors.

Administration of 5-10 mg/kg of phencyclidine (PCP) caused stereotyped behaviors including sniffing, backpedalling, head weaving and turning in rats. The PCP-induced stereotyped behaviors (backpedalling, head weaving and turning) were attenuated by serotonin (5-HT) depleters [reserpine, p-chlorophenylalanine, p-chloroamphetamine (PCA)] and 5-HT receptor antagonist (cyproheptadine). PCP-induced head weaving and turning were potentiated by 5-HT precursor (tryptophan) and 5-HT releaser (PCA). PCP-induced head weaving were potentiated also by monoamine oxidase inhibitor (pargyline) and 5-HT reuptake inhibitor (imipramine). PCP 5-10 mg/kg significantly increased the content of 5-HT in the thalamus/hypothalamus at 30 and 60 min after the injection, except PCP 5 mg/kg at 60 min. PCP 7.5 and 10 mg/kg increased the rate of increment of 5-HT by pargyline in the thalamus/hypothalamus at 30 and 60 min after the injection, respectively. PCP 10 mg/kg significantly increased the contents of 5-HIAA in the striatum and thalamus/hypothalamus at 30 min, but decreased that of 5-HIAA in all discrete brain areas except the stratium at 60 min after the injection. PCP also significantly prevented the depletion of 5-HT by PCA in all discrete brain areas except the stratium at 60 min after the injection. From these results, PCP-induced stereotyped behaviors are related to an increased serotonergic neuronal activity due to 5-HT releasing action and/or inhibitory action of 5-HT uptake-by this drug.

Animals↗

PubMed1984

Design of a phencyclidine implantation pellet; suitable for tolerance development.

When using laboratory animals (e.g., mice) for phencyclidine (PCP) tolerance studies, an essential part of the procedure is to administer the PCP in such a way that the animals received adequate doses of the drug at frequent enough intervals to reach and maintain the desired levels of tolerance or employ a osmotic minipump which is either suitable or convenient to develop a high degree of tolerance to PCP in a large number of animals in a short period. However, these methods are unfit for routine work because of repeated daily injections consume too much time and osmotic minipump comes expensive. Therefore, in this paper we attempted to develop PCP pellet suitable for tolerance development. The s.c. implantation of a 10 or 20 mg PCP pellet in the back of a conscious mouse resulted in a much more rapid development of tolerance to PCP than that produced in mice receiving daily i.p. injection of, 10 or 20 mg/kg, PCP-HCl. Assessment of and degree of tolerance to PCP by PCP pellet implantation and daily injection of PCP-HCl were evidenced by a degree of decrease in the duration of motor incoordination after the challenge with, 20 mg/kg, PCP-HCl 24 h after removal of PCP pellets or a last injection of PCP-HCl. These studies may demonstrate a substantial methodological improvement in producing a high degree of tolerance to PCP in a short period of time by means of the s.c. pellet implantation technique.

Animals↗

PubMed1984

[Phencyclidine, a drug which induces psychosis: its neuropharmacological actions].

Phencyclidine (PCP) is a major drug of abuse as well as a 'drug of choice' among substance abusers in the U. S. A. Unfortunately, PCP use may result in the development of psychotic behavior. PCP-induced psychosis is characterized by confusion, excitation, aggression, paranoia, hallucinations and delusions of grandeur and may evoke violent or suicidal behavior. Therefore, many patients suffering from PCP-induced psychosis have been diagnosed initially as schizophrenic. However, PCP-related research has not kept pace with the rise in abuse and PCP-induced psychosis. The neurochemical effects of PCP are not well defined at present, but both behavioral and biochemical studies suggest that it may interact with dopaminergic, cholinergic, noradrenergic, serotonergic, GABAergic and enkephalinergic systems. In addition, the specific reversible, saturable, high affinity 3H-PCP binding site is discovered recently in rat brain. On the other hand, there is now a large body of evidence to suggest that opiate receptors may be subdivided into mu, sigma, kappa and delta receptors. On the basis of behavioral and binding studies, it is proposed that the sigma receptor and the PCP binding site are one and the same. This receptor interacts with PCP and psychotomimetic opioids to produce their psychotomimetic effects. In connection with this receptor, a trial to isolate an endogenous ligand produces psychotomimetic effects, "angeldustin" is progressing. This review has served to illustrate the paucity of information currently available on the central effects of PCP. However, our current notions of the mechanisms of action of PCP are very complicate. Such a review inevitably raises more question than it answers but it is hoped that these may stimulate further investigation in this field.

Acetylcholine↗

PubMed1983

Phencyclidine-induced stereotyped behaviors in rats following specific neurotoxin lesions of the striatum.

All the components of phencyclidine(PCP)-induced stereotyped behaviors, including sniffing, backpedalling, turning and head weaving were significantly decreased in rats following kainic acid lesion of the striatum. In the 6-hydroxydopamine lesioned rats, the behavioral score of PCP-induced stereotyped sniffing was similar to that in the sham-operated rats, while other components were significantly decreased. In addition, only the PCP-induced backpedalling and head weaving were significantly attenuated in the 5,6-dihydroxytryptamine lesioned rats. These results suggest that not only dopaminergic but also serotonergic and other systems in the striatum may play important roles in PCP-induced stereotyped behaviors.

5,6-Dihydroxytryptamine↗