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Biomedical subjects

S Tadokoro

Publications and source records attributed to S Tadokoro.

At least 55 records · Page 3Linked to original sources
PubMed1992

Ethanol enhances, but diazepam and pentobarbital reduce the ambulation-increasing effect of caffeine in mice.

The interactions of caffeine (10 mg/kg p. o.) with various doses of ethanol, diazepam or pentobarbital were investigated by observing the ambulatory activity of mice. The ambulatory activities after the coadministration of caffeine with ethanol (1.6, 2.4 and 3.2 g/kg p. o.) were significantly higher than those after the single administration of the corresponding doses of individual drugs. Ethanol alone significantly increased the activity with ataxia at 2.4 and 3.2 g/kg, suggesting that 1.6 g/kg of ethanol was an optimum dose for studying the interaction of caffeine with ethanol. Although diazepam (0.25, 0.5 and 2 mg/kg s. c.) and pentobarbital (1, 3 and 10 mg/kg s. c.) alone did not change the activity, they significantly reduced the effect of caffeine. Naloxone (1 and 5 mg/kg s. c.) did not modify the effect of caffeine alone, but, at 5 mg/kg, it was effective in significantly reducing the ambulation-increasing effect of caffeine with ethanol (1.6 g/kg) to nearly the level of caffeine alone. Ca-cyanamide (5 mg/kg p. o., pretreatment 30 min before), reserpine (1 mg/kg s. c., pretreatment 4 hr before) and alpha-methyl-p-tyrosine (200 mg/kg i. p., pretreatment 1 hr before) reduced the ambulation increment induced by caffeine alone or combination of caffeine with ethanol. Ethanol, diazepam and pentobarbital are classified as CNS depressants, and caffeine as a CNS stimulant. However, the present experiment demonstrated that the interaction of caffeine with ethanol was very different from that of caffeine with diazepam or pentobarbital. In the enhancing interaction of caffeine and ethanol, both dopaminergic and endogenous opioid systems may be involved.

Animals↗
PubMed1992

[Behavioral study on reduction of psychotic and behavioral disorders induced by antitussive and expectorant].

Previously, we reported that psychotic and behavioral disorders induced by repeated abuse of a commercial preparation of antitussive and expectorant (BRON-W Solution, SS Pharmaceut.) was mainly due to caffeine (CAF). In order to reduce such problem, we assessed effects of a preparation containing theophylline (THEO) as the substitution of CAF, and dihydrocodeine (2HCOD), methylephedrine (MEPH) and chlorpheniramine (CPA) on ambulatory activity and discrete lever-press avoidance response in mice. It is well known that THEO is less potent in the central action than CAF, but its relaxant action on smooth muscle is about 2 times as potent as that of CAF. Therefore, the dose of THEO administered was half of that of CAF. A significant increase in the ambulatory activity was produced by the administration of CAF and/or mixed preparations, in which CAF was contained with 2HCOD, MEPH and CPA at the same doses with those in BRON 10 ml/kg. The ambulation-increasing effects of THEO and THEO-containing preparations were less potent than those of CAP and CAF-containing preparations. Furthermore, repeated 5 times administration of CAF-containing 4-drug preparation (CAF + 2HCOD+MEPH+CPA) elicited a progressive enhancement of the ambulation-increasing effect. Whereas, almost the same effect was reproduced throughout the 5 times administration of THEO-containing 4-drug preparation (THEO + 2HCOD+MEPH+CPA). The discrete lever-press avoidance response was disrupted (i.e., decrease in the avoidance rate) by CAF-containing preparations. However, THEO-containing preparations did not induce such disruption of the avoidance response, but rather improved the avoidance response (i.e., increase in the avoidance rate).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Behavioral effects of cocoa and its main active compound theobromine: evaluation by ambulatory activity and discrete avoidance in mice.

Effects of cocoa and its main CNS active constituent methylxanthine theobromine as well as caffeine were evaluated by ambulatory activity, and discrete lever-press and shuttle avoidance in mice. Cocoa (1 g/kg p.o.) and theobromine (10 mg/kg p.o.) significantly increased ambulatory activity. However, the other doses of cocoa and theobromine had no effect on the ambulatory activity. Caffeine increased ambulatory activity with the maximum action at 30 mg/kg p.o. Furthermore, cocoa (0.1, 0.3 and 1 g/kg), theobromine (3, 10, 30 and 100 mg/kg) and caffeine (3, 10, 30 and 100 mg/kg) enhanced the ambulation-increasing effect of methamphetamine (2 mg/kg s.c.). The ambulation-increasing effect of cocaine (20 mg/kg s.c.) was also enhanced by cocoa (1 g/kg), theobromine (10, 30 and 100 mg/kg) and caffeine (10, 30 and 100 mg/kg). On the other hand, comparatively higher doses of theobromine and caffeine disrupted the well established avoidance response. Thus, the avoidance rate was significantly decreased by theobromine (100 mg/kg and more) and caffeine (30 mg/kg and more) under the lever-press situation, and by theobromine (100 mg/kg and more) and caffeine (100 mg/kg) under the shuttle situation. These dose effect relationships revealed that cocoa contains about 1% theobromine. The present results indicate that we may receive the CNS action of theobromine through consumption of theobromine-containing foodstuffs or beverages in our every day life.

Animals↗
PubMed1992

Sensitization to ambulation-increasing effects of cocaine after repeated administration in mice--roles of dose and interval of administration as well as experimental environments.

Effects of 5 subcutaneous injections of cocaine (COC) at 10, 20 or 40 mg/kg at intervals of 1 to 7 days were investigated by placing mice individually into tilting activity cages (20cm in diameter and 18 cm height). A progressive enhancement of the ambulation-increasing effect was noted for 3 to 4 hrs after each administration, showing marked sensitization (reverse tolerance). The enhancement of the effect progressed rapidly and the maximum sensitization was observed after the 3rd to 4th administration of 10 to 20 mg/kg at intervals of 3 to 7 days. The peak effect of the enhancement was of short duration. Sensitization lasted for at least one month. However, 40 mg/kg of COC produced stereotyped behaviors concurrent with preconvulsive signs which were also enhanced by serial administration. In contrast, pretreatment with COC in a narrow environment (glass jar, 5.5 cm in diameter and 15 cm height) did not cause the enhancement to the ambulation-increasing effect of the drug. Cross-sensitization was observed from COC to methamphetamine.

Animals↗
PubMed1991

Comparison of sensitization to ambulation-increasing effects of cocaine and methamphetamine after repeated administration in mice.

The effects of repeated (5 times) subcutaneous administration of cocaine (10, 20 or 40 mg kg-1) and methamphetamine (1, 2 or 4 mg kg-1) at 3-4 day intervals have been compared in mice placed individually into tilting activity cages. A progressive enhancement of the ambulation-increasing effect was noted for 3-4 h after each administration, indicating that sensitization occurred. This occurrence and the existence of an optimal dose producing sensitization were similar for both drugs. However, enhancement of the effect after cocaine progressed rapidly and maximum sensitization was observed earlier than after methamphetamine administration. Moreover, the higher doses of cocaine (40 mg kg-1) caused stereotypies concurrent with preconvulsive signs of short duration that were enhanced by serial administration. In contrast, methamphetamine caused a more progressive enhancement, but stereotypies with no preconvulsive signs were produced by the higher dose (4 mg kg-1). The respectively, effective doses for the development of enhancement suggested that cocaine was less potent than methamphetamine in producing sensitization. Cross-sensitization occurred between both drugs. Thus, sensitization to cocaine was distinct from that to methamphetamine due to differences in its rapidity, intensity, and the presence or absence of preconvulsive changes.

Animals↗
PubMed1991

[Behavioral effects of febarbamate (MS-543): evaluation by ambulatory activity, active avoidance and passive avoidance in mice].

Febarbamate (MS-543: 100 and 10000 mg/kg, p.o.) neither produced significant change in the mouse's ambulatory activity after the single administration nor modified the ambulation-increasing effects of the following drugs: methamphetamine (2 mg/kg, s.c.), apomorphine (0.5 mg/kg, s.c.) and scopolamine (0.5 mg/kg, s.c.). MS-543 (100 and 1000 mg/kg, p.o.) scarcely affected the established active avoidance response in mice under a discrete shuttle avoidance situation. However, MS-543 (1000 mg/kg, p.o.) tended to enhance the decrease in response and/or avoidance rates induced by chlorpromazine (2 mg/kg, s.c.) and physostigmine (0.2 mg/kg, s.c.). Finally, the disruption of the step-through passive avoidance response induced by pre-training administration of scopolamine (0.5 mg/kg, s.c.) in a one trial task was reduced when MS-543 was administered before the scopolamine administration. However, the post-training administration of MS-543 was without effect on the scopolamine-induced disruption of the avoidance. Furthermore, no significant effect of MS-543 was observed in the multi-trial passive avoidance task. The present results suggest that MS-543 activates cholinergic function and possesses a slight sedative action.

Animals↗
PubMed1991

Enhancement of the ambulation-increasing effect of opioid analgesics by ethanol in mice.

The interaction between opioid analgesics (morphine and buprenorphine) and central depressants (ethanol, pentobarbital and diazepam) was investigated by means of ambulatory activity in mice. The ambulation-increasing effect of both morphine (10 mg/kg, s.c.) and buprenorphine (1 mg/kg, s.c.) was enhanced by the combined administration of ethanol (0.8-3.2 g/kg, p.o.) in a dose-dependent manner. Naloxone (0.1 mg/kg, s.c.) was effective for reducing the enhanced ambulatory activity. The pretreatment with Ca-cyanamide (5 mg/kg, p.o., 30 min before) reduced the enhancement of the ambulation-increasing effect induced by the combined administration of opioid analgesics with ethanol, although it scarcely modified that of morphine and buprenorphine alone. On the other hand, neither pentobarbital (1-30 mg/kg, s.c.) nor diazepam (0.25-2 mg/kg, s.c.) modified markedly the ambulation-increasing effect of morphine and buprenorphine. The present results suggest that ethanol specifically interacted with opioid analgesics when the mouse's ambulatory activity was used as the indicator.

Animals↗
PubMed1991

Differential antagonism of the stimulant effects of MK-801 and methamphetamine by ceruletide: evaluation by discrete shuttle avoidance response in mice.

A noncompetitive NMDA antagonist MK-801 (0.03-0.3 mg/kg, i.p.) increased the response rate of mice trained under the discrete shuttle avoidance situation to a degree similar to the increase by methamphetamine (0.1-1 mg/kg, i.p.). The cholecystokinin-like decapeptide ceruletide significantly reduced the response-increasing effect of MK-801 (0.1 mg/kg) at 0.001 micrograms/kg; however, only 10 micrograms/kg of ceruletide, which per se inhibited the response, attenuated that of methamphetamine (0.3 mg/kg). The coadministration of MK-801 (0.1 mg/kg) and methamphetamine (0.3 mg/kg) produced no potentiation of the effect, and almost the same effect was maintained even after the additional administration of ceruletide (0.1 microgram/kg).

Animals↗
PubMed1991

Differential sensitization to ambulation-increasing effect of methamphetamine after repeated administration to mice in activity cages of different sizes.

We have demonstrated that repeated administration of methamphetamine (MAP) 1-2 mg/kg, s.c. in a tilting-type round activity cage with a diameter of 20 cm (20 cm-cage) at 1-7 day intervals produces progressive enhancement of the ambulation-increasing effect (AIE), showing sensitization (reverse tolerance) in mice. However, almost no sensitization was observed when mice had been pretreated with the same doses of MAP but confined in a narrow environment repeatedly. In this experiment, changes in the sensitization were investigated in mice after repeated pretreatments with MAP at 2 mg/kg at 3-4 day interval for 4 times in activity cages of 5 different sizes (5, 10, 15, 30 and 40 cm in diameter) in comparison with that of in the 20 cm-cage. AIE obtained after MAP in the 5- and 10-cm cages was not enhanced, whereas AIE was significantly enhanced in the cages of more than 15 cm in diameter. There was no significant difference in the enhanced AIE among the 4 groups that received the same pretreatment repeatedly in the cages of 15, 20, 30 and 40 cm in diameter. The present results suggest that in accordance with the all-or-none law, development of the sensitization is affected by the size of the activity cage in which the animals have repeatedly experienced the acute drug effect.

Animals↗
PubMed1991

[Changes in rhythmicity of ambulatory and drinking activities in immature female rats].

Adult female rats showed increase in ambulatory activity and marked decrease in drinking behavior at early dark period (18:00-24:00) of proestrus stage before ovulation. In this study, we observed the changes in patterns of ambulatory and drinking activities of immature rats associated with estrous cycle during growing period. Immature female rats of the Wistar-Imamichi strain were used, and both behavioral activities were measured continuously, using Gundai type Ambulodrinkometer. From these observations, it was found that the typical patterns of ambulatory and drinking activities which were observed in adult female rats appeared at the sixth (51-60 days old) and the third (39-49 days old) estrous cycle, respectively.

Animals↗
PubMed1991

[Course and morphology studies in penile cancer].

A 75-year-old male patient showed an extensive erosion mainly restricted to the penile site, which was found when he received appendectomy. The penile lesion had persisted for about ten years, during which period the erosion extended gradually while he missed to consult a physician. The lesion was a florid and wetting erosion, with a definite boundary, which covered the entire circumference of the penile foreskin and also extended to the suprapubic area, scrotum and external urethral orifice. Although the diagnosis could not be made by biopsy, extra mammary Paget's disease was strongly suspected. Bilateral modified inguinal lymphadenectomy and systemic evaluation were first performed to confirm that there was no metastasis or complexed disease in other organs. Then extensive wide resection of the skin lesion and reconstruction using a split-thickness skin graft were performed. Histopathological examination of the surgical specimen revealed poorly differentiated squamous cell carcinoma, although most part showed only inflammatory erosion. Clinical course and the histopathological findings including specific staining patterns led to the diagnosis of poorly differentiated squamous cell carcinoma originated from erythroplasia. During post-operative 18 months until now, no local recurrence or distant metastasis has been observed.

Aged↗
PubMed1991

[Radical surgery with pubectomy for primary male posterior urethral cancer--a case report].

A 38-year-old male patient with the past history of polioencephalopathy was admitted with urinary retention and high grade fever. Although he was able to walk he had the intelligence of a 3-year-old child and his spine, thorax, fingers were deformed remarkably. Immediately after the admission, cystostomy was carried out and 600 ml of stinky and cloudy urine was noted. Although intensive antibiotic therapy was performed, high grade fever with leucocytosis (greater than 15,000/mm2) persisted for more than 10 days. Retrograde urethrogram showed stricture in the anterior urethra as well as irregular filling defect in the bulbomembranous urethra. After urethral dilation using urethral dilators, 18Fr nephrostomy balloon catheter was indwelled and the patient was discharged. However, the urethral irregular filling defect was unchanged and cytological examination of urine and urethral secretions revealed class V. After the readmission, endoscopic examination revealed papillary tumor lesions occupying the whole posterior urethra were found. With the diagnosis of invasive posterior urethral cancer, anterior exenteration by en bloc pubectomy, pelvic lymphadenectomy and ileal conduit urinary diversion were carried out. On the surgical specimen, the tumor occupied the bulbomembranous and prostatic urethra. Histopathological diagnosis was TCC G3 greater than SCC, stage B. Since the tumor invaded the serosa of the membranous urethra, we thought it could not be removed completely without the pubctomy.

Adult↗
PubMed1991

[Modification of stereotypy-producing and ambulation-increasing effects following repeated administration of methamphetamine in rats].

Effects of repeated administration of methamphetamine (MAP: 1.25, 2.5 and 5 mg/kg, sc) at an interval of 4 days for 10 times on stereotyped behaviors as well as ambulatory activity in adult male rats of Wistar strain were investigated. In the first administration of MAP 1.25 mg/kg, marked ambulation-increasing effect was observed mixing with simple stereotyped behaviors such as sniffing and head-bobbing. The stereotypy-producing effect of MAP was apparently observed in a dose-dependent manner, and complicated stereotyped behaviors such as head-weaving and licking simultaneously with sniffing and head-bobbing were frequently demonstrated when 5 mg/kg of MAP was first administered. Furthermore, the ambulation-increasing effect after the drug showed biphasic pattern, i.e. pre-stereotypic and post-stereotypic increases in ambulatory activity, because the activity was interfered by the stereotyped behaviors. When MAP was administered repeatedly, the sniffing- and head-bobbing-producing effects were selectively enhanced at any dose, showing sensitization phenomenon (reverse tolerance), and the pre-stereotypic increase in ambulatory activity was inhibited, while the post-stereotypic increase was progressively enhanced. Although the sensitized stereotypy-producing effect was observed more markedly in the 10th administration of MAP 2.5 mg/kg than that in the first administration of MAP 5 mg/kg, the complicated stereotyped behaviors were hardly seen. It is suggested that the sensitization effects are not always identical qualitatively with the effects observed after increase in MAP-dose.

Animals↗
PubMed1991

Modifications of ambulation-increasing effect of morphine and buprenorphine following repeated administration in mice.

Interaction of behavioral effects of morphine (10 and 20 mg/kg s. c.) and buprenorphine (0.3 and 1 mg/kg s. c.) were investigated by means of ambulatory activity following repeated administration of either drug in mice. The repeated administration of buprenorphine (1 mg/kg, but not 0.3 mg/kg) total of 5 times at intervals of 3-4 days induced a gradual decrease in the sensitivity to its ambulation-increasing effect. The buprenorphine-experienced mice showed an increase in the sensitivity to the ambulation-increasing effect of morphine (20 mg/kg) in parallel with the doses of buprenorphine. On the other hand, the ambulation-increasing effect of morphine (10 and 20 mg/kg) progressively enhanced during the repeated administration schedule. The morphine-experienced mice demonstrated a decrease in the sensitivity to buprenorphine (1 mg/kg). The present results may reflect differential characteristics between morphine and buprenorphine in their ambulation-increasing effects in mice.

Animals↗
PubMed1991

Effects of repeated administration of buprenorphine on ambulatory activity in mice.

Effects of repeated administration of buprenorphine, given 5 times at intervals of 3-4 days, were investigated by ambulatory activity in mice. Buprenorphine (0.3 and 1 mg/kg sc) significantly increased the activity, and tolerance to the effect tended to be produced during the repeated administration schedule. The mice that experienced the repeated administration of buprenorphine exhibited an increased sensitivity to the ambulation-increasing effect of methamphetamine (2 mg/kg) in parallel with the doses of buprenorphine. However, no significant modification of the sensitivity to buprenorphine was produced in the mice that had experienced the repeated methamphetamine administration. Furthermore, the established reverse tolerance to methamphetamine was not significantly modified by the repeated treatment with buprenorphine (0.1, 0.3 and 1 mg/kg).

Animals↗
PubMed1991

The ambulation-increasing effect of buprenorphine in mice: comparison with the effect of morphine.

Effects of buprenorphine on ambulatory activity in mice were studied, and the result s were compared with those of morphine. Buprenorphine, at 0.01-3 mg/kg s.c., increased the mouse's ambulatory activity in a dose-dependent manner with Straub tail-reaction. The effect reached to the maximum level at 10-20 min and persisted for 2-3 hr after the administration. The overall activity counts for 3 hr were almost identical when 1 mg/kg of buprenorphine and 10 mg/kg of morphine were administered. Naloxone, 0.01-1 mg/kg s.c., reduced the ambulation-increasing effect of both buprenorphine and morphine, but the reducing-action of naloxone was stronger for morphine than for buprenorphine. However, the combined administration of buprenorphine and morphine demonstrated no significant modification in individual drug effects. On the other hand, the ambulation-increasing effect of buprenorphine and morphine were enhanced by combined s.c. administration of methamphetamine (1 mg/kg), cocaine (10 mg/kg), scopolamine (0.5 mg/kg), or caffeine (10 mg/kg). Such enhancing effects of methamphetamine and cocaine were much greater for buprenorphine than for morphine. In contrast, haloperidol (0.05 mg/kg), pilocarpine (2 mg/kg), and N6-(L-2-phenylisopropyl)-adenosine (0.1 mg/kg) reduced the ambulation-increasing effect of buprenorphine or morphine. The modification by pilocarpine was more marked for morphine than for buprenorphine. The present results indicate that buprenorphine and morphine possess differential effectiveness on dopaminergic and/or cholinergic systems.

Animals↗
PubMed1990

[Modification of the behavioral effects of drugs after repeated administration--special reference to the reverse tolerance of amphetamines].

It has been well-known that a chronic abuse of amphetamines induces schizophrenia-like psychotic symptoms, namely amphetamine psychosis. When amphetamines are repeatedly administered to rodents, a reverse tolerance (behavioral sensitization) to the ambulation-increasing and/or stereotypy-producing effect is observed. The process of the reverse tolerance is affected by various factors. A clear reverse tolerance is produced when optimal doses of the drug (2 mg/kg, s.c. for mice, and 0.5-1 mg/kg, s.c., for rats) is administered at intervals of longer than 1 day rather than a shorter interval. Furthermore, the animal has to be put into a freely mobile situation during the presence of the acute drug effect. A cross reverse tolerance is observed between certain types of drugs that show an ambulation-increasing effect, although the potencies are different among the drugs. A reverse tolerance to the stereotypy (in particular sniffing and head-bobbing)-producing effect is also observed when comparatively higher doses of methamphetamine are repeatedly administered. The process is qualitatively identical with the reverse tolerance to the ambulation-increasing effect produced by the repeated administration of comparatively smaller doses. The reverse-tolerance, once established, to both ambulation-increasing and stereotypy-producing effects is almost irreversible even with various treatments such as repeated post-treatment with antipsychotics. The characteristics of reverse tolerance to methamphetamine in animals might be closely correlated to the amphetamine psychosis in humans. It is also necessary to search for a method that effectively reduces the established reverse tolerance to amphetamines.

Age Factors↗