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T Nabeshima

Publications and source records attributed to T Nabeshima.

At least 343 records · Page 19Linked to original sources
PubMed1987

Phencyclidine-induced head-twitch response in rats treated chronically with methysergide.

This study was designed to assess whether phencyclidine (PCP)-induced behaviors in rats were potentiated after two days' withdrawal from chronic methysergide (a 5-HT2 receptor blocker) treatment (10 mg/kg per day i.p. for 12 days), in order to confirm the involvement of 5-hydroxytryptamine (5-HT) neurons in PCP actions. The PCP (10 mg/kg)-induced behaviors (head-twitch, head-weaving, turning and backpedalling) were attenuated by successive pretreatment with PCP (10 mg/kg per day i.p. for 12 days), while PCP- and 5-methoxy-N,N-dimethyltryptamine (2 mg/kg)-induced head-twitch increased significantly after the repeated methysergide treatment was stopped. The development of tolerance to PCP-induced head-twitch was antagonized by pretreatment with methysergide. Furthermore, Scatchard plots of specific [3H]ketanserin binding at the 5-HT2 receptors and [3H]PCP binding at the PCP receptors in the methysergide group revealed significant increases in binding capacity (Bmax) with no change in affinity (Kd). On the contrary, after development of tolerance to PCP, there were significant decreases in Bmax of [3H]ketanserin binding with no change in affinity. PCP can thus displace [3H]ketanserin at the 5-HT2 receptor site, but not [3H]5-HT at the 5-HT1 receptor site. These facts indicate that PCP may produce head-twitch via an agonistic interaction with 5-HT2 receptor sites.

Animals↗
PubMed1987

Antinociceptive activity induced by tizanidine and alpha 2-adrenoreceptors.

Tizanidine [5-chloro-4-(2-imidazolin-2-yl-amino)-2,1,3-benzothiadiazole] is able to increase the pain threshold in the tail-flick test in mice. The effect of tizanidine was investigated after treatment of mice with drugs influencing central monoaminergic and GABAergic mechanisms. A drug that inhibits the synthesis and storage of monoamines and drugs that cause specific lesions of monoaminergic neurons had no consistent effect on the antinociceptive action of tizanidine. The action of tizanidine was antagonized by the alpha 2-adrenoreceptor antagonist, yohimbine, but not by the alpha 1 antagonist prazosin, nor by dopamine, serotonin and GABA receptor antagonists. These results indicate that the antinociceptive action induced by tizanidine may be mediated by alpha 2-adrenoreceptors.

Analgesics↗
PubMed1987

Phencyclidine-induced head-weaving and head-twitch through interaction with 5-HT1 and 5-HT2 receptors in reserpinized rats.

Phencyclidine mainly produced head-weaving and head-twitches at doses of 5-7.5 mg/kg and of 7.5-12.5 mg/kg, respectively. Phencyclidine-induced head-twitches and head-weaving were blocked by pretreatment with ritanserin (1 mg/kg), a selective serotonin (5-HT)2 receptor antagonist and with pindolol (20 mg/kg, s.c.), a 5-HT1 receptor antagonist, respectively. In reserpine-pretreated rats, the degree of utilization of 5-HT and the number of 5-HT1 ([3H]5-HT) and 5-HT2 ([3H]ketanserin) binding sites were significantly increased compared with the figures for the vehicle-pretreated rats. The intensity of phencyclidine-induced head-weaving (at the dose of 2.5 mg/kg) and head-twitch (at the doses of 2.5 and 5 mg/kg) was significantly increased in reserpine-pretreated rats compared with that of vehicle-pretreated rats. Furthermore, in the reserpine-pretreated rats, the intensity of phencyclidine (1.25 mg/kg)-induced head-weaving and head-twitches was increased in combination with imipramine, while the intensity of phencyclidine (2.5 mg/kg)-induced head-weaving and head-twitch was decreased by pretreatment with mianserin, a non-selective 5-HT receptor antagonist. These results indicate that phencyclidine induced head-weaving by interacting with 5-HT1 receptors, indirectly after the release of 5-HT and/or with some other mechanisms and induced head-twitch by interacting with 5-HT2 receptors directly and/or indirectly.

Animals↗
PubMed1987

Effects of prenatal and perinatal administration of phencyclidine on the behavioral development of rat offspring.

The effects of prenatal and perinatal administration of a nonteratogenic dose of phencyclidine (PCP) on the behavioral development of Sprague-Dawley rats were examined. In the offspring prenatally treated with PCP (10 mg/kg) between days 7 and 17 of gestation, a decrease in maternal body weight in the gestation period, a decrease in fetal body weight and body length, a decrease in viability of offsprings, and a decrease in the body weights of the offspring in the nursing period were observed. Furthermore, PCP pups had difficulty performing the rota-rod task at 4 weeks and exhibited a decrease in sensitivity to challenged PCP at 5 weeks (female). In the offspring prenatally treated with PCP between days 7 and 21 of gestation, a decrease in the body weights of dams, fetuses and offspring, and a decrease in the viability of offsprings were observed. PCP pups showed an increase in the score for head-twitch response (male), a delay in the development of ambulation, negative geotaxis (male), bar holding and rope-descending behavior (female). However, the PCP administration during prenatal (between days 17 and 21 of gestation) and nursing periods showed only a decrease in viability and body weight of offspring, and a delay in the development of the separation of eyelids. These results suggest that more attention should be given to the developmental toxicity of PCP.

Animals↗
PubMed1987

Different effects of ethylketocyclazocine on phencyclidine- and N-allylnormetazocine-induced stereotyped behaviors in rats.

The effects of ethylketocyclazocine (EKC) on the stereotyped behaviors induced by intraperitoneal injection of phencyclidine (PCP) or N-allylnormetazocine (SKF 10,047) were examined. EKC markedly antagonized PCP-induced stereotyped behaviors such as sniffing, head-weaving, turning and backpedalling. On the other hand, EKC failed to antagonize SKF 10,047-induced stereotyped behaviors, which are PCP-like stereotyped behaviors, except sniffing and head-weaving at 0-15 min after the SKF 10,047 injection. PCP-induced turning and backpedalling were potentiated by pretreatment with SKF 10,047, while PCP-induced sniffing and head-weaving were not. EKC failed to affect the enhancing effect of SKF 10,047 on PCP-induced turning and backpedalling. These results suggest that part of the PCP- and SKF 10,047-induced stereotypy may be mediated by different neuronal mechanisms.

Analgesics, Opioid↗
PubMed1987

[Behavioral pharmacological action of Ca-4-(3,5-dihydroxy-3-methylpenthylamido) butyrate (mevalonic GABA, MV-GABA)].

The behavioral pharmacological effects of Ca-4-(3,5-dihydroxy-3-methylpenthylamido) butyrate (mevalonic-GABA, MV-GABA), a new GABA derivative were studied in comparison with those of Ca-hopantenate (HOPA) in mice. MV-GABA had no effect on the general behavior and electric shock-induced fighting behavior. The dosage of MV-GABA which caused locomotor hypoactivity produced an impairment of the rotarod performance. MV-GABA inhibited the hyperactivity induced by a dopamine (DA) agonist (methamphetamine) and acetylcholine (ACh) antagonists (scopolamine and atropine) at a dose which did not affect locomotor activity in normal mice. MV-GABA prolonged the pentobarbital-Na-induced sleeping time, and it prolonged the latencies until convulsion and death after administration of strychnine. MV-GABA and HOPA antagonized the electroconvulsive shock-induced amnesia in the passive avoidance response of mice. These results suggest that MV-GABA has effects on the central nervous systems, in particular, ACh and DA neural systems. The actions of MV-GABA were qualitatively similar to those of HOPA except for the effect on the DA neural system.

Agonistic Behavior↗
PubMed1987

Potentiation in phencyclidine-induced serotonin-mediated behaviors after intracerebroventricular administration of 5,7-dihydroxytryptamine in rats.

Phencyclidine (PCP)-induced behaviors were compared with 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)- and p-chloroamphetamine-induced behaviors in rats pretreated with ritanserin or 5,7-dihydroxytryptamine (5,7-DHT) in order to investigate whether PCP interacts with 5-hydroxytryptamine2 (5-HT2) receptors. Head-twitch and wet-dog shake induced by p-chloroamphetamine, a 5-HT releaser, and head-twitch induced by PCP were blocked completely by pretreatment with ritanserin, a specific 5-HT2 receptor blocker, but other behaviors induced by p-chloroamphetamine, PCP and 5-MeODMT, a 5-HT agonist, were not. The intensity of head-weaving, turning, backpedalling and hind-limb abduction induced by 5-MeODMT and the intensity of head-weaving, turning and head-twitch induced by PCP were markedly greater in the rats 2 weeks after the 5,7-DHT, a 5-HT neurotoxin-injection. Contrarily, 5-HT-mediated behaviors induced by p-chloroamphetamine were attenuated in the 5,7-DHT-treated rats. 5,7-DHT-treatment increased the number of 5-HT1 ([3H]-5-HT), 5-HT2 ([3H]ketanserin) and PCP ([3H]PCP) binding sites in the synaptic membrane of rat brain, but decreased the brain level of 5-HT (41% of control). These results may indicate that PCP as a 5-HT2 agonist induces head-twitch via 5-HT2 receptors, and that PCP induces head-weaving and turning via 5-HT1 receptors and/or some other mechanisms in rats.

5,7-Dihydroxytryptamine↗
PubMed1987

Analgesic and antiinflammatory effects of 2-(10,11-dihydro-10-oxo-dibenzo[b,f]thiepin-2-yl)propionic acid in rat and mouse.

Analgesic and antiinflammatory effects of 2-(10,11-dihydro-10-oxo-dibenzo[b,f]thiepin-2-yl)propionic acid (CN-100) have been investigated pharmacologically in rats and mice. With bradykinin-induced pain responses, CN-100 proved to be the most potent of the commercial non-steroidal antiinflammatory drugs which were tested in rats: The potency of CN-100 was 4 times stronger than that of indometacin. The analgesic effect of CN-100 on writhing induced by acetic acid, adjuvant-induced hyperalgesia, and carrageenin-induced hyperalgesia, and the effect on AgNO3-induced arthralgia were equipotent to or a little weaker than those of indometacin, but stronger than that of diclofenac sodium. In mice, CN-100 was found to be as active as indometacin against peritonitis induced by acetic acid and pain responses induced by mechanical stimulus (pressure). Against the peritonitis induced by acetylcholine and phenyl-quinone, CN-100 showed inhibitory actions and its potencies were much stronger than those of aminophenazone (amino-pyrine) in mice. However, all the drugs tested failed to increase pain thresholds induced by thermal stimulus in rats and mice. CN-100 exerted potent inhibitory effects on carrageenin-induced acute inflammatory edema and adjuvant-induced arthritis. The antiinflammatory effect of CN-100 on the former was equal to that of indometacin, but weaker on the latter. The ulcerogenic activity of CN-100 was less potent than that of indometacin. These results indicate that CN-100 may produce its analgesic effects through a peripheral mechanism and be preferable for clinical use, especially for the treatment of inflammatory conditions accompanied by pain.

Acetylcholine↗
PubMed1986

A role played by dopamine and opioid neuronal systems in stress-induced motor suppression (conditioned suppression of motility) in mice.

Mice exhibited a marked suppression of motility (conditioned suppression of motility, which is one of stress-induced motor suppressions) when placed in the same chamber where they had previously received an electric footshock. In the present study the role played by dopamine and opioid neuronal systems in the conditioned suppression of motility has been investigated. In conditioned suppression group, the contents of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and methionine-enkephalin (Met-enk) did not change in the hypothalamus, cerebral cortex and medulla oblongata/pons, while a decrease in the contents of striatal DOPAC were induced compared to that in the control group, which was accompanied by reduction in the contents of Met-enk. In addition, the contents of DA were increased in the midbrain. The ratio of DA metabolites/DA contents in the striatum of the conditioned suppression group was decreased. In the striatum, moreover, the depletion of DA induced by alpha-methyl-p-tyrosine (alpha-MT) in the conditioned suppression group was significantly lower than that in the control group but not in the midbrain. These results suggest that the DA turnover rate and Met-enkergic activity decrease in the striatum of conditioned suppression group.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Methysergide-induced precipitated withdrawal syndrome in phencyclidine-dependent rats.

Chronic phencyclidine (PCP) administration has been shown to produce tolerance to a number of its pharmacological actions. We have suggested that PCP interacts with the 5-HT2 receptors since it inhibits [3H]spiperone binding to 5-HT2 receptors in vitro. In the present study, we investigated whether methysergide (a 5-HT2 receptor blocker) induces the precipitated withdrawal syndrome in PCP-tolerant rats. The body weight of the rats in the abrupt and precipitated withdrawal groups was significantly lower 5 days and 1-5 days after withdrawal, respectively, than that in the control group. Furthermore, other typical precipitated abstinence syndrome characteristics such as jumping, wet-dog shake and ptosis were also observed in the precipitated withdrawal group. These results suggest that PCP produces its behavioral effects via an agonistic interaction with 5-HT2 receptor sites and that our method may be very useful for the development of a rat model for studying physical dependence on PCP.

Animals↗
PubMed1986

Phencyclidine-induced stereotyped behaviors after injection of ethylketocyclazocine, Mr 2266 and naltrexone in rats.

The effects of ethylketocyclazocine (EKC), Mr 2266 and naltrexone on the stereotyped behaviors induced by an intraperitoneal injection of phencyclidine (PCP) were examined. PCP-induced turning, backpedalling, head weaving and sniffing were antagonized by pretreatment with EKC (0.25-4.0 mg/kg). While pretreatment with Mr 2266 (2.5 mg/kg), a kappa selective antagonist, and naltrexone (10 mg/kg), a mu selective antagonist, failed to affect the PCP-induced stereotypy, Mr 2266 antagonized the suppressing effect of EKC on PCP-induced stereotypy. Taken into consideration, this suggests that kappa opioid agonists such as EKC antagonize PCP-induced stereotyped behaviors through a kappa opioid mechanism, and that the mu opioid receptor may not play an important role in the PCP-induced stereotypy in rats.

Animals↗
PubMed1986

Comparison of alpha-adrenoceptor involvement in the antinociceptive action of tizanidine and clonidine in the mouse.

The effect of drugs that influence the opioidergic and monoaminergic neuronal systems on the antinociceptive action of tizanidine [5-chloro-4-(2-imidazolin-2-yl-amino)-2,1, 3-benzothiodiazole] was compared with their effect on the action of clonidine. The potency of the clonidine-induced antinociceptive action was 1.83 and 7.75 times greater than that of tizanidine in the tail-flick and acetic acid-induced writhing tests, respectively. The action of tizanidine and clonidine was completely antagonized by pretreatment with yohimbine, an alpha 2-adrenoceptor blocker, but not by prazosin, an alpha 1-adrenoceptor blocker. Other alpha-adrenoceptor blockers, phenoxybenzamine and phentolamine, also attenuated the action of tizanidine and clonidine but the potency of these drugs was less than that of yohimbine. An opioid antagonist (naloxone), drugs influencing the serotonergic neuronal system (p-chlorophenylalanine, 5,6-dihydroxytryptamine, cyproheptadine), and drugs influencing the catecholaminergic system (alpha-methyl-p-tyrosine, diethyl-dithiocarbamate, 6-hydroxydopamine, haloperidol) showed no effect on the action of tizanidine and clonidine. From these results, it appears that alpha 2-adrenoceptors might be of importance in mediating the tizanidine and clonidine antinociceptive action in the tail-flick test.

Acetates↗
PubMed1986

Potentiation of phencyclidine-induced stereotyped behaviors in rats by thiorphan and bestatin.

We investigated the effects of thiorphan, a specific inhibitor of enkephalinase A and bestatin, a specific inhibitor of aminopeptidase, on the stereotyped behaviors induced by phencyclidine (PCP) in cannulated rats. The PCP-induced turning was significantly potentiated when thiorphan (50 micrograms) and bestatin (50 micrograms) were injected simultaneously into the rat lateral ventricle. The increase of PCP-induced turning was completely antagonized by the pretreatment with naloxone. Thiorphan (50 micrograms) or bestatin (50 micrograms) alone failed to potentiate PCP-induced turning. Thiorphan and/or bestatin did not affect significantly the PCP-induced head weaving and back-pedalling except that thiorphan (50 micrograms) potentiated the PCP-induced head weaving 15-18 min after the PCP injection. The combination of thiorphan and bestatin alone did not induce any behavioral change. These results suggest that thiorphan and bestatin produce an increase of endogenous enkephalins and that as a result, PCP-induced turning may be enhanced.

Amino Acids, Sulfur↗
PubMed1986

Involvement of spinal and supraspinal structures in tizanidine-induced antinociceptive action.

The site of action of tizanidine (5-chloro-4-(2-imidazolin-2-yl-amino)2,1,3-benzothiadiazole) was investigated in a tail-flick test in comparison with clonidine and morphine. Tizanidine and clonidine produced a profound and linear dose-dependent antinociceptive action by i.c.v. administration. The ED50 values for tizanidine, clonidine and morphine were increased 2-4-fold 1 or 3 days after spinalization at C5-C6. These results indicate that the antinociceptive activity of tizanidine arises mainly from activity at the supraspinal level, similar to clonidine and morphine, but these drugs act also at the spinal level at high doses.

Animals↗
PubMed1986

Phencyclidine-induced retrograde amnesia in mice.

The amnesic action of phencyclidine (PCP) was investigated in mice using a passive avoidance- and escape-learning method. PCP (10-30 mg/kg) administered immediately after the training test dose-dependently shortened and prolonged the step-down latency and escape latency, respectively in the retention test. There was a significant inverse relationship between the step-down and escape latencies, indicating that PCP had induced amnesia. The amnesic actions of PCP were retrograde, being observed when mice were given PCP within 10 min but not more than 30 min after the training test. The amnesic effects of PCP on both variables were antagonized significantly by physostigmine and naloxone, whereas cyproheptadine and haloperidol had no effect. None of these drugs by themselves affected passive avoidance- or escape-learning performance. These results suggest that the retrograde amnesic actions of PCP were produced via either the cholinergic or the opioidergic systems or both, but not through the serotonergic and the dopaminergic systems.

Amnesia↗
PubMed1986

The antagonistic effects of naloxone on cycloheximide and anisomycin-induced amnesia.

The amnesia induced by cycloheximide (CXM) injected SC and by CXM or anisomycin injected ICV immediately after the training test was antagonized in combination with an opiate antagonist, naloxone (NLX). This antagonism occurred on both the passive avoidance- and escape-learning responses in a dose-dependent manner in mice. NLX alone (0.3-10.0 mg/kg) did not alter the performances of these tasks. Furthermore, the decrease in retention performance on shuttle avoidance in rats induced by CXM was also antagonized by NLX. Treatment with CXM and/or NLX did not affect spontaneous locomotor activity. The interaction of these drugs on the performance of the passive avoidance- and escape-learning and the shuttle avoidance tasks may be related to neurochemical memory processes. These results suggest that an opioid system may participate in the amnesic actions induced by protein synthesis inhibitors in these models.

Amnesia↗
PubMed1986

Phencyclidine-induced wet-dog shakes observed in rats after withdrawal from reserpine treatment.

This study was designed to assess the involvement of serotonergic neurons in phencyclidine (PCP)-induced wet-dog shakes in rats after termination of reserpine treatment. Administration of L-5-hydroxytryptophan (7.5-12.5 mg/kg) to rats 30 min following pretreatment with pargyline induced wet-dog shakes which included head shake and whole body shake. p-Chloroamphetamine (PCA) (5 mg/kg) alone also produced wet-dog shakes in the vehicle-pretreated rats, but PCP (2.5-7.5 mg/kg) and tryptophan (100 mg/kg) alone did not. The number of wet-dog shakes significantly increased after the injection of PCA (2.5 and 5 mg/kg) in the reserpine-pretreated rats, in which the 5-hydroxyindoleacetic acid/serotonin (5-HT) ratio was significantly higher and postsynaptic 5-HT receptors were also in a state of supersensitivity, compared to that of the vehicle-pretreated rats. PCP (2.5-7.5 mg/kg) also produced wet-dog shakes in a dose-dependent fashion in rats after pretreatment with reserpine. Furthermore, PCP-induced wet-dog shakes were potentiated by imipramine, a 5-HT-uptake blocker, and prevented by mianserin, a 5-HT receptor-blocker. Tryptophan (100 mg/kg) alone produced wet-dog shakes in the reserpine-pretreated rats and it was enhanced in combination with imipramine. These results may indicate that the PCP-induced wet-dog shakes after reserpine withdrawal are due to an increased release of 5-HT from the functional pool and supersensitivity of postsynaptic 5-HT receptors.

Animals↗