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Biomedical subjects

S Tadokoro

Publications and source records attributed to S Tadokoro.

At least 37 records · Page 2Linked to original sources

Circulating thrombopoietin level in chronic immune thrombocytopenic purpura.

The circulating thrombopoietin (TPO) level in 43 patients with chronic immune thrombocytopenic purpura (ITP) was examined by an ELISA system. The TPO level (mean +/- SD) in ITP patients was mildly elevated (1.86 +/- 1.17 fmol/ml) compared to that in normal subjects (0.76 +/- 0.21), and was within the normal range in 30% of ITP patients. In contrast, the TPO level in patients with aplastic anaemia was very high, 12.35 +/- 6.42 fmol/ml. There was no correlation between TPO level and platelet count in ITP patients. Splenectomy was performed in two ITP patients, after which platelet counts increased to normal levels and TPO levels showed a transient increase. These data suggest that reactive TPO production against thrombocytopenia in ITP is small when compared to that in aplastic anaemia. Relative endogenous TPO deficiency may play some role in the pathophysiology of thrombocytopenia in ITP patients.

Adult↗

Long-continuous observation of the effects of methamphetamine on wheel-running and drinking in mice.

1. Effects of methamphetamine (MAP) on wheel-running and drinking in mice, housed under 12-hr light-dark schedule (light period; 06:00-18:00), were investigated through long-continuous observation. 2. MAP (1, 2 and 4 mg/kg, s.c.) acutely increased the wheel-running and drinking for 2-4 hr in a dose-dependent manner after the administration at 11:00, midpoint of light period. 3. MAP administered at 11:00 sub-acutely suppressed the spontaneous increment during dark period (18:00-06:00) in both the behaviors. 4. Many factors, such as the time-of-day and interval of the administration as well as the dose administered, affected the behavioral suppression induced by MAP. 5. In addition to these findings, the wheel-running and drinking during the light period increased even on the days without MAP administration. 6. These results suggest that MAP have not only acute stimulant and sub-acute depressant effects, but also long-lasting effects.

Animals↗

Effect of chlorpromazine on mouse ambulatory activity sensitization caused by (+)-amphetamine.

The development of sensitization to the ambulation-increasing effect of (+)-amphetamine (2.5 mg kg-1) was found to be dose-dependently inhibited when 1 or 2 mg kg-1 chlorpromazine was administered concomitantly, and the sensitization to (+)-amphetamine was almost completely suppressed when co-administered with 4 mg kg-1 chlorpromazine. Following a challenge dose of 2.5 mg kg-1 (+)-amphetamine, mice pretreated with (+)-amphetamine alone or with (+)-amphetamine plus 1 or 2 mg kg-1 chlorpromazine showed similar marked enhancement of the sensitization. However, mice that had been given (+)-amphetamine plus 4 mg kg-1 chlorpromazine displayed only slight enhancement of the effect compared with the activity level in saline-pretreated mice.

Amphetamine↗

Effect of OM-853, a cerebral metabolic ameliorator, on ambulatory activity and passive and active avoidance responses in mice and Mongolian gerbils.

Behavioral effects of OM-853 were investigated in both mice and Mongolian gerbils. In mice, OM-853 alone produced no marked change in the ambulatory activity, although it tended to lower it at 100 mg/kg, and this drug (5-100 mg/kg, p.o.) reduced the ambulation-increasing effect of scopolamine (0.5 mg/kg, s.c.) in a dose-dependent manner. Moreover, OM-853 (50 and 100 mg/kg, p.o.) prolonged the latency times shortened by scopolamine under the passive avoidance. On the other hand, in the discrete avoidance situation, OM-853 facilitated the acquisition of shuttle avoidance at 10 and 25 mg/kg, p.o. and lever-press avoidance at 25 and 50 mg/kg, p.o. in the pre-training administration schedule, and the former at 25-100 mg/kg, p.o. and the latter at 10 and 25 mg/kg, p.o. in the post-training administration schedule. In gerbils, OM-853 (50 mg/kg, i.p.) ameliorated the learning deficit of the lever-press avoidance response induced by forebrain ischemia. The present results suggest that OM-853 has beneficial actions on some types of learning and memory in normal, scopolamine-treated and ischemic animals. The possible mechanisms involved are discussed.

Animals↗

Effects of repeated MK-801 on ambulation in mice and in sensitization following methamphetamine.

The noncompetitive NMDA receptor antagonist MK-801, (+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]-cyclohepten-5,10-imine , increased ambulatory activity in the mouse at doses over 0.1 mg/kg (IP). The effect was enhanced when 0.3 mg/kg MK-801 was repeatedly administered at intervals of 3-4 days. In contrast, a reduction of the effect was induced with repeated doses of 0.1 and 1 mg/kg. The mice that had repeatedly experienced 1 mg/kg MK-801 exhibited a decrease in the sensitivity to methamphetamine (2 mg/kg SC). In addition, the repeated co-administration of 1 mg/kg MK-801 with methamphetamine induced a decrease in the sensitivity to methamphetamine. No modification of methamphetamine sensitivity was elicited by 0.1 and 0.3 mg/kg MK-801 in both the single and co-administration schedules. On the other hand, established sensitization to methamphetamine was hardly affected by repeated treatment with 0.1-1 mg/kg MK-801. These results indicate that the mechanism of the inhibitory action of MK-801 on the development of methamphetamine sensitization is different from that of dopamine D2 antagonists, which may act to decrease the effective unit dose of methamphetamine and reduce ambulation-increasing effect of methamphetamine.

Animals↗

Aspects of animal experiments for evaluation of cognitive enhancers: in particular, the behavioral characteristics of Mongolian gerbils.

1. The step-through passive avoidance response and discrete lever-press avoidance response of Mongolian gerbils were evaluated to point out the basic problems in the learning and memory tests in this species. 2. Mongolian gerbils exhibited extremely poor acquisition and maintenance of the passive avoidance response. 3. In contrast to the result under the passive avoidance situation, Mongolian gerbils demonstrated an excellent performance under the discrete lever-press avoidance situation. 4. A 5-min brain ischemia elicited a severe morphological damage of the pyramidal cells in hippocampal CA1 region. 5. A small part of such ischemic animals showed a deficit of acquisition of the discrete lever-press avoidance. 6. These results suggest that there is merit and demerit of the acquisition dependent on the type of tasks, and that the brain function of Mongolian gerbils may be maintained even after the ischemic operation.

Animals↗

Circadian variation in R-THBP-induced enhancement of the ambulation-increasing effect of methamphetamine on mice.

6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R-THBP), a co-factor for tyrosine hydroxylase and tryptophan hydroxylase, induces the enhancement of ambulation-increasing effect of methamphetamine on mice. In this study, we investigated the circadian variation in the interaction between R-THBP and methamphetamine by changing the time-of-day of both methamphetamine administration and pretreatment with R-THBP. The mouse's ambulatory activity was measured by a tilting-type activity cage for 4 hr. In the daytime, but not in the nighttime, the ambulation-increasing effect of methamphetamine (1 and 2 mg/kg, s.c.) was significantly enhanced by the pretreatment with R-THBP (100 mg/kg, s.c., 2 or 6 hr before). These data indicate the possibility that peripherally administered R-THBP increases the biosynthesis of catecholamine especially in the daytime.

Analysis of Variance↗

[Effects of mosapramine (Y-516), a new dopamine D2 antagonist, on reverse tolerance after repeated administration of methamphetamine by means of the ambulation-increasing effect in mice].

Effects of mosapramine (Y-516), a new dopamine D2 antagonist, on reverse tolerance (sensitization) after repeated administration of methamphetamine (MAP; 2 mg/kg, s.c.) were investigated by means of ambulatory activity in mice; and they were compared with those of clocapramine (CCP), bromperidol (BPD) and chlorpromazine (CPZ). Y-516 (0.3, 1, 3 and 10 mg/kg, p.o.), CCP (3, 10 and 30 mg/kg, p.o.), BPD (0.1, 0.3 and 1 mg/kg, p.o.), CPZ (1, 3 and 10 mg/kg, p.o.) or 0.5% methylcellulose (MC; solvent, p.o.) were given to mice 30 min before MAP administration. The ambulatory activity was measured by tilting-type activity changes for 3 hr after MAP. These treatments were repeated 5 times at 3-4 day intervals. Then MAP alone was challenge-administered to all of these mice 3-4 days after the final administration. Marked reverse tolerance was produced after repeated administration of MC plus MAP. On the other hand, the ambulation-increasing effect of MAP was suppressed dose-dependently in groups pretreated with Y-516 or comparison-drugs, although the development of reverse tolerance was not completely inhibited after the repeated administration. In the challenge-administration of MAP, the ambulation-increasing effect was dose-dependently suppressed in the Y-516 group or the comparison-drug plus MAP group as compared with that in the MC plus MAP group.

Animals↗

Characteristics of the ambulation-increasing effect of the noncompetitive NMDA antagonist MK-801 in mice: assessment by the coadministration with central-acting drugs.

Characteristics of the ambulation-increasing effect of MK-801, a non-competitive NMDA antagonist, were assessed through the coadministration of MK-801 with various central-acting drugs in mice. The MK-801 (0.3 mg/kg, i.p.)-induced ambulation-increment with a slight ataxia was maximum at around 50 min, and ambulation returned to the control level at about 3 hr after the administration. At 1 mg/kg, the mouse's activity transiently increased, followed by a decrease due to a marked ataxia, which was due to neither stereotypy nor convulsion, for 20-50 min, and then increased again; the ambulation-increment continued even at 4 hr after the administration. Coadministration of MK-801 (0.3 mg/kg, i.p.) with either methamphetamine (2 mg/kg, s.c.), cocaine (20 mg/kg, s.c.), GBR-12909 (10 mg/kg, i.p.), scopolamine (0.5 mg/kg, s.c.), caffeine (10 mg/kg, s.c.) or morphine (10 mg/kg, s.c.) produced a significant enhancement of the effect. However, 0.1 mg/kg of MK-801 had no effect on the interaction with these drugs. On the other hand, the ambulation-increasing effect of MK-801 (0.3 mg/kg) was significantly reduced by haloperidol (0.3 and 0.1 mg/kg, s.c.), ceruletide (0.01 and 0.1 mg/kg, i.p.), reserpine (0.05 and 2 mg/kg, s.c., pretreatment 4 hr before) and nimodipine (1 and 3 mg/kg, i.p.), but it was scarcely modified by alpha-methyl-p-tyrosine (100 and 200 mg/kg, i.p., pretreatment 24 hr and 4 hr before), imipramine (20 mg/kg, i.p.), 6R-L-erythro-5,6,7,8-tetrahydro-biopterin (100 mg/kg, i.p.), pilocarpine (1 and 4 mg/kg, s.c.), N6-(L-2-phenylisopropyl)-adenosine (0.03 and 0.1 mg/kg, s.c.) and naloxone (1 and 5 mg/kg, s.c.).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Caffeine does not effectively ameliorate, but rather may worsen the ethanol intoxication when assessed by discrete avoidance in mice.

Ethanol disrupted the discrete lever-press and shuttle avoidances in mice at doses over 1.6 and 2.4 g/kg, p.o., respectively, eliciting a dose-dependent decrease in the % of avoidance with no significant change or slight increase in the response rate. Caffeine increased the response rate of both the avoidances at the doses of 1-30 mg/kg, p.o., but disrupted the avoidance at 100 mg/kg. Caffeine (10 mg/kg) reduced the decreased % of avoidance by ethanol (1.6 and 2.4 g/kg) with a significant increase in the response rate. In contrast, the % of avoidance was significantly lower after the combined administration of ethanol (3.2 g/kg) with caffeine than after ethanol (3.2 g/kg) alone. Unlike ethanol, diazepam (2 mg/kg, s.c.) and pentobarbital (10 mg/kg, s.c.) significantly decreased both the response rate and the % of avoidance. Caffeine (10 mg/kg) ameliorated the decreased response rate and the % of avoidance produced by diazepam and pentobarbital. The present results suggest that caffeine does not effectively ameliorate, but rather may worsen the ethanol intoxication.

Alcoholic Intoxication↗

Assessment of the ambulation-increasing effect of ketamine by coadministration with central-acting drugs in mice.

The coadministration of ketamine (12.5 mg/kg, but not 3.1 mg/kg, s.c.) with methamphetamine (2 mg/kg, s.c.), cocaine (10 mg/kg, s.c.), scopolamine (0.5 mg/kg, s.c.), caffeine (10 mg/kg, s.c.) and MK-801 (0.1 mg/kg, i.p.) significantly enhanced the ambulation-increasing effects. Furthermore, in the coadministration with morphine (10 mg/kg, s.c.) and GBR-12909 (10 mg/kg, i.p.), not only 12.5 mg/kg but also 3.1 mg/kg of ketamine produced a significant enhancement. On the other hand, the ambulation-increasing effect of ketamine (12.5 mg/kg, s.c.) was significantly suppressed by ceruletide (0.01 mg/kg, i.p.), alpha-methyl-p-tyrosine (100 and 300 mg/kg, i.p. x 2), nimodipine (1 and 3 mg/kg, i.p.), haloperidol (0.03 and 0.1 mg/kg, s.c.), a low dose of apomorphine (0.1 mg/kg, s.c.), physostigmine (0.1 mg/kg, s.c.) and N6-(L-2-phenylisopropyl)-adenosine (0.1 mg/kg, s.c.). However, imipramine (20 mg/kg, i.p.), 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (100 mg/kg, s.c.), a high dose of apomorphine (0.5 mg/kg), reserpine (0.3 and 1 mg/kg, s.c.), propranolol (0.3 and 1 mg/kg, s.c.), phenoxybenzamine (3 and 10 mg/kg, s.c.) and naloxone (0.3 and 1 mg/kg, s.c.) scarcely interacted with ketamine. These results suggest that ketamine increases the ambulatory activity in mice by facilitating dopamine release from a newly synthesized pool at the presynaptic level, which is affected by a calcium-dependent mechanism.

Animals↗

[Changes in rhythmicity of ambulatory and drinking activities produced by presentation of short time lightings during dark period in rats].

It is well known that the lighting conditions affect many physiological phenomenon of laboratory animals. However, lighting conditions are frequently disturbed by investigators themselves. In this study, behavioral (ambulation and drinking) rhythmicities of rats were investigated after irregular lighting; i. e. presentation of short time lighting at 21:00, 24:00 and 3:00 for 12 min during dark period (18:00-6:00). Vaginal smear was taken and sexual cycle was observed everyday. Ambulatory and drinking activities were measured by Gundai type Ambulo-drinkometer. The irregular lighting produced the following changes in the rhythmicities: 1) increase in the ambulatory activity during 15:00-18:00 immediately before dark period 2) decrease in ambulatory activity before ovulation 3) disappearance of inhibitory phenomenon of drinking activity which was usually observed before ovulation 4) increase in the drinking activity during 6:00-9:00 immediately after dark period 5) the changes in rhythmicities of the behavioral activities lasted for more than 1 month after replacement to the regular lighting condition.

Animals↗

Changes in rhythmicities of ambulatory and drinking activities after hypophysectomy in rats.

Effects of hypophysectomy on circadian rhythms of ambulatory and drinking activities in adult male rats were automatically recorded and investigated with a Gundai-type ambulodrinkometer. The rats were maintained under LL conditions following an LD condition. When free-running rhythms had stabilized, the rats were hypophysectomized. The rhythmicities of both activities became indistinct over the 2-4 weeks following surgery, and then gradually recovered. At this time phase shifts (phase advance) were observed in the hypophysectomized rats, while these changes were not observed in sham-operated rats. All rats entrained to lighting when kept under LD conditions again. These results suggest that the pituitary does not play an essential role in maintaining circadian rhythms, but does function as an important subordinal oscillator.

Animals↗

Behavioral evaluation of psycho-pharmacological and psychotoxic actions of methylxanthines by ambulatory activity and discrete avoidance in mice.

The behavioral effects of methylxanthines, caffeine, theophylline and theobromine, were compared by means of ambulatory activity and discrete lever-press avoidance response in mice. The single oral administration of 10-100 mg/kg of caffeine, 30-300 mg/kg of theophylline, and 10 mg/kg of theobromine significantly increased the mouse's ambulatory activity. However, 1000 mg/kg of theobromine decreased the activity. The ambulation-increasing effect of methamphetamine (2 mg/kg s.c.) was enhanced by coadministration with caffeine (3-100 mg/kg), theophylline (10-300 mg/kg), and theobromine (10-100 mg/kg). On the other hand, comparatively higher doses of caffeine (up to 30 mg/kg) slightly but significantly decreased the avoidance rate without eliciting any significant change in the response rate. Theobromine significantly decreased the response rate at higher than 300 mg/kg, and the avoidance rate at higher than 100 mg/kg. Furthermore, 1000 mg/kg of theobromine was much toxic for mice, i.e., half mice died within a few hr after the end of the 1-hr avoidance session. Theophylline did not produce any significant change in the avoidance response at the dose range of 3-300 mg/kg. These results may indicate the relative order of the centrally stimulant and/or behavioral toxic actions of methylxanthines in human.

Animals↗

[Effects of nicotine on circadian rhythm of ambulatory activity and drinking in rats].

Effects of the intake of nicotine solution and/or forced administration of nicotine at a fixed time-of-day on circadian rhythm of ambulatory activity and drinking in rats were observed under various conditions. Rats showed nocturnal pattern under the light-dark cycle (L: D = 12:12, light period 6:00-18:00), and the patterns scarcely altered while the rats were given 150 micrograms/ml of nicotine solution. When a restricted feeding only for 1 h per day (10:00-11:00) was loaded to the rats, the ambulatory activity and drinking appeared in the light period, especially around the feeding time. While rats were given 15-150 micrograms/ml of nicotine solution under the restricted feeding condition, they demonstrated a marked phase-shift in the circadian rhythm in the concentration-dependent manner. Rats showed free-running rhythms with tau value of longer than 24 h under the constant red dim light condition (CRDL), and such rhythm was scarcely modified by the intake of nicotine solution of 50-150 micrograms/ml. However, when nicotine (1.5 mg/kg po), but not tap water, was administered at 10:00 every day under the CRDL condition, it also produced phase-shift which was similar to that induced by the nicotine ingestion under the redose of nicotine is administered or taken at a fixed time-of-day.

Administration, Oral↗