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S Tadokoro

Publications and source records attributed to S Tadokoro.

At least 73 records · Page 4Linked to original sources

[Characteristics of antagonism between ceruletide and various central-acting drugs: investigation by means of ambulatory activity in mice].

Behavioral characteristics of ceruletide, a cholecystokinin-like decapeptide, were investigated by means of ambulatory activity in mice. Ceruletide at 100 and 300 micrograms/kg, i.p. slightly but significantly decreased the mouse's activity for 20 min. Therefore, 100 micrograms/kg of ceruletide was used in the experiment of combined administration with the central-acting drugs. Ceruletide reduced the increased activity which was produced by methamphetamine (2 mg/kg, s.c.), ephedrine (80 mg/kg, i.p.), methylphenidate (4 mg/kg, s.c.), cocaine (20 mg/kg, s.c.), mazindol (2.5 mg/kg, s.c.), apomorphine (0.5 mg/kg, s.c.), bromocriptine (8 mg/kg, i.p.), scopolamine (0.5 mg/kg, s.c.), caffeine (10 mg/kg, s.c.) and morphine (20 mg/kg, s.c.) with different potencies and durations. The mice that had experienced ceruletide at 3 micrograms/kg for 5 times at intervals of 3-4 days demonstrated a significant increase in the sensitivity to methamphetamine, although the same treatment with 10-300 micrograms/kg of ceruletide was without effect. On the other hand, when 3-300 micrograms/kg of ceruletide was combined with 2 mg/kg of methamphetamine, the development of reverse tolerance to the ambulation-increasing effect of methamphetamine was inhibited dependently on the doses of ceruletide. However, the reverse tolerance to methamphetamine once established was scarcely modified by ceruletide when it was administered afterwards.

Animals↗

Effects of YM-09151-2, a potent and selective dopamine D2 antagonist, on the ambulation-increasing effect of methamphetamine in mice.

The ambulation-increasing effect of methamphetamine (2 mg/kg, s.c.) was markedly reduced by YM-09151-2 at 0.01 mg/kg, s.c., in drug-naive mice. The development of reverse tolerance to the ambulation-increasing effect of methamphetamine was also inhibited almost completely when 0.01 mg/kg, s.c., of YM-09151-2 was administered concomitantly in each administration. However, YM-09151-2, at 0.01 mg/kg, was partially suppressed the effect of methamphetamine in mice that exhibited reverse tolerance to methamphetamine.

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Cross interaction between methamphetamine and scopolamine by means of ambulatory activity in mice.

Interaction between methamphetamine (MAP; 1 and 2 mg/kg, s.c.) and scopolamine (SCP; 0.5 and 2 mg/kg, s.c.) was investigated by means of ambulatory activity in mice of the dd strain. The single administration of MAP and SCP increased the ambulatory activity in a dose-dependent manner. The repeated administration of SCP, 5 times at intervals of 3-4 days, elicited a tolerance to its ambulation-increasing effect. The SCP-experienced mice showed no marked change in their sensitivity to the ambulation-increasing effect of MAP. However, when MAP was additionally administered, these mice showed a reverse tolerance to MAP. Such repeated administration of MAP was effective for attenuating the SCP-tolerance. On the other hand, the repeated MAP administration produced not only reverse tolerance to MAP itself but also cross reverse tolerance to SCP. However, as observed in the drug-naive mice, the MAP-experienced mice also exhibited tolerance to the additionally administered SCP. The repeated SCP administration scarcely modified the acquired MAP-reverse tolerance. The present results suggest that a cross reverse tolerance from MAP to SCP, but not from SCP to MAP, is developed in this mouse strain. It is also suggested that the reverse tolerance to MAP and tolerance to SCP appear regardless of the pretreatment of SCP and MAP, respectively, and that the reverse tolerance to MAP is well-maintained.

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Behavioral study on mergocriptine (CBM36-733) by ambulatory activity in mice: repeated administration and interaction with methamphetamine.

Effects of repeated administration of mergocriptine (CBM36-733: CBM), a long-acting ergot derivative with an agonistic action on both dopamine D1 and D2 receptors, as well as interaction between CBM and methamphetamine (MAP: 2 mg/kg, s.c.), were investigated by ambulatory activity in mice. CBM at 4 mg/kg significantly suppressed the ambulatory activity, but significantly increased it at 16 mg/kg in the drug-naive mice. However, 4 and 8 mg/kg of CBM were effective for increasing the ambulatory activity when these doses were repeatedly administered for 9 times at intervals of 7 days. The same treatment with 16 mg/kg of CBM produced a reverse tolerance to the ambulation-increasing effect. The mice that had received CBM at 1 and 2 mg/kg, but not 4-16 mg/kg, demonstrated a significantly lower sensitivity to MAP than the saline-experienced mice. On the other hand, the repeated MAP administration induced not only a reverse tolerance to itself, but also a cross reverse tolerance to 8 and 16 mg/kg of CBM. Furthermore, the established reverse tolerance to MAP was scarcely attenuated by the repeated treatment with any doses of CBM, but rather enhanced by 8 and 16 mg/kg of CBM. The present results indicate that, although the dose-effect relations are partially different, the behavioral characteristics of CBM were almost identical with those of bromocriptine, another long-acting ergot derivative having antagonistic and agonistic actions on dopamine D1 and D2 receptors, respectively.

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The anticonflict effect of MK-801, an NMDA antagonist: investigation by punishment procedure in mice.

The NMDA antagonist MK-801 at 0.3 mg/kg, i.p. increased the punished response under a MULT VI 1.5/FR 5-punishment schedule of food reinforcement in mice. Furthermore, although neither MK-801 (0.1 mg/kg, i.p.) nor diazepam (0.25 mg/kg, s.c.) was without effect when separately administered, a significant increase in the punished response appeared after the combined administration of these two drugs. The present results suggest that MK-801 not only shows an anticonflict effect, but also enhances the anticonflict effect of benzodiazepine anxiolytics in mice.

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Effects of ceruletide, administered singly and in combination with central-acting drugs, on discrete shuttle avoidance response in mice.

The single administration of ceruletide at 10-300 micrograms/kg, i.p., slightly but significantly decreased the response rate (frequency of shuttles) under a discrete avoidance task in mice. Over 10 micrograms/kg of ceruletide attenuated the increase in the response rate induced by methamphetamine (0.5 mg/kg, s.c.). However, ceruletide, at 1-300 micrograms/kg, did not significantly enhance the response- and/or avoidance-decreasing effects of chlorpromazine (1 mg/kg, s.c.), haloperidol (0.1 mg/kg, s.c.), pilocarpine (4 mg/kg, s.c.) and N6-(L-2-phenylisopropyl)-adenosine (0.1 mg/kg, s.c.), but rather tended to reduce the avoidance-decreasing effect of chlorpromazine and pilocarpine at 1-100 micrograms/kg.

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Effects of repeated administration of pentazocine on ambulatory activity in mice: comparison with the effects of morphine and methamphetamine.

Effects of single and repeated administration of pentazocine (5 times at intervals of 3-4 days) were compared with those of morphine and methamphetamine by means of ambulatory activity in mice. The interactions among these 3 drugs were also investigated. Pentazocine (25 mg/kg, s.c.), morphine (10 and 20 mg/kg, s.c.) and methamphetamine (2 mg/kg, s.c.) significantly increased the activity, and the effect progressively enhanced (defined here as development of reverse tolerance) during the repeated administration schedule. The induction of reverse tolerance to pentazocine was less dependent on the environmental conditions, and it was abolished within 2 months. A cross reverse tolerance was demonstrated from methamphetamine to pentazocine and to morphine, and from morphine to pentazocine. However, no significant cross reverse tolerance was induced from pentazocine to morphine and to methamphetamine, and from morphine to methamphetamine. The present results suggest that pentazocine possesses an ambulation-increasing effect, although the characteristics are different from that of either morphine or methamphetamine.

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Unpleasant and anticonflict effects of nicotine observed by conditioned taste aversion and hypertonic NaCl solution tests in mice.

Effects of subcutaneously (s.c.) administered nicotine on preference for 0.1% saccharin solution and rejection for hypertonic (2%) NaCl solution were investigated in water-deprived mice. The results were compared with those after s.c. administration of methamphetamine, caffeine and morphine. When nicotine 0.3 and 1 mg/kg, methamphetamine 0.5, 1 and 2 mg/kg, and caffeine 30 mg/kg were administered to mice immediately after intake of the saccharin solution, they exhibited a significant decrease in the preference for saccharin solution on the next day (namely conditioned aversion), even though no drug administration was carried out. However, 2.5-10 mg/kg of morphine produced no marked change in the preference. Daily administration for 5 days of nicotine 1 mg/kg, methamphetamine 2 mg/kg, caffeine 30 mg/kg, and morphine 10 mg/kg did not produce any marked change in the individual drug effects on the conditioned taste aversion. On the other hand, rejection for the hypertonic NaCl solution was significantly attenuated when nicotine 0.3 mg/kg was administered prior to the experiment, probably showing an anticonflict effect. Caffeine 10 mg/kg, and morphine 2.5 and 5 mg/kg also attenuated the rejection for hypertonic NaCl solution. In contrast, methamphetamine 0.25-2 mg/kg enhanced the rejection in a dose-dependent manner. The present results suggest that, in spite of the same dose, nicotine shows both unpleasant and anticonflict (antianxiety) effects dependent on the environmental situation such as stimulus, timing of the drug administration etc. Furthermore, it is notable that the effects of nicotine observed in our experiments were similar to those of caffeine.

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[A case of everting ectopic ureterocele in child--controversy in the surgical treatment].

A 4-year-old girl with the history of repeated urinary tract infections was referred from the pediatric department to our department on January, 1987. Under the diagnosis of right ectopic ureterocele of everting type with complete duplication of renal unit, the one-stage operation, that is, right hemi-nephroureterectomy with complete excision of the ureterocele and ureteral stump was carried out on January 27, 1987. Reimplantation of the orthotopic mate ureter was done because of injury to lower part of the mate ureter during operation, although reflux of the mate ureter did not exist. After the operation, the voiding symptom became better except for large residual urine volume (300 ml). In order to protect renal function, intermittent catheterization was carried out. Two years and 8 months after that operation, residual urine volume was reduced to 20 ml. Judging from the literature and our experience, if the patient is not in a severe condition, we recommend one-stage operation, that is, total correction (a single operation designed to correct abnormalities of the upper and lower urinary tract) for ectopic ureterocele in children.

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Effects of psychoactive drugs on the conflict behavior under operant situation in Mongolian gerbils (Meriones unguiculatus).

Effects of diazepam, pentobarbital, morphine, ethanol, caffeine, and nicotine on the conflict behavior established under a MULT FR 20/FR 20 punishment schedule of food reinforcement were investigated in Mongolian gerbils. Fourteen out of 17 gerbils learned lever-press response for food within 15 sessions of training under FR 20 schedule. Although high voltage of electric shock (125-225 V) was required for attaining lever-press suppression, all 14 gerbils exhibited stable conflict behavior, i.e., showing high response rate of 20-30 responses/min in the safety period and low response rate of 0-3 responses/min in the alarm period. Diazepam, a prototype of the antianxiety drugs, increased the response rate in the alarm period. The anticonflict effect was also observed after administration of either pentobarbital or ethanol. On the other hand, morphine suppressed lever-pressing in a nonspecific manner. Caffeine tended to attenuate the conflict behavior, but nicotine had no such effect. These results suggest that the effects of psychoactive drugs on the conflict behavior of gerbils are almost identical with those in mice and rats.

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[Behavioral effects of NC-1100, 1-(3,4-dimethoxyphenyl)-2-(4-diphenylmethylpiperazinyl) ethanol dihydrochloride--on ambulatory activity, discrete lever-press response and shuttle avoidance response in mice].

Single administration of NC-1100 (3, 10 or 30 mg/kg, p.o.) produced no marked change in the ambulatory activity and discrete lever-press avoidance response. However, 100 mg/kg of this drug produced a toxic effect which was characterized by salivation, tremor, clonic convulsion, etc., but none of the mice died. NC-1100 enhanced the ambulation-increasing effect of methamphetamine (2 mg/kg, s.c.) at 3 and 10 mg/kg, while it failed to modify that of scopolamine (0.5 mg/kg, s.c.). NC-1100, at 100 mg/kg, suppressed both the established discrete lever-press and shuttle avoidance responses, probably due to non-specific and toxic effects. When NC-1100 at 10 mg/kg was administered, the response rate increased only in the shuttle avoidance situation in which the avoidance established mice were used. Furthermore, when NC-1100 at 30 mg/kg was administered immediately before the start of the training session, the avoidance rate increased. However, there was no marked change in the avoidance rate in the 2nd training session which was conducted 24 hr after the 1st training session without the drug administration. Additionally, the response rate increased in the 1st and 2nd training sessions after 10 and 30 mg/kg of NC-1100. The present results suggest that NC-1100 may show a behavior-facilitating effect, although its effect is mild and different from that of typical central stimulants such as methamphetamine.

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Reverse tolerance to ambulation-increasing effects of methamphetamine and morphine in 6 mouse strains.

Effects of single administration of methamphetamine (1, 2 and 4 mg/kg, s.c.) and morphine (5, 10 and 20 mg/kg, s.c.) and repeated administration of methamphetamine (2 mg/kg, s.c.) and morphine (10 mg/kg, s.c.) on ambulatory activity were investigated in 6 mouse strains: dd, ICR, BALB/c, C57BL/6, C3H/He and DBA/2. Although there were differences in the drug sensitivities among mouse strains, methamphetamine and morphine increased the ambulatory activity in all the strains except for the DBA/2 strain that showed an increase only after morphine. Repeated 5 times administration of methamphetamine at intervals of 3-4 days induced a reverse tolerance (an enhancement in the sensitivity) to the ambulation-increasing effect in all the strains with a marked degree in dd, ICR, C3H/He and DBA/2 strains and a slight degree in BALB/c and C57BL/6 strains. The same treatment with morphine induced reverse tolerance to the effect of morphine markedly in C57BL/6 and C3H/He strains and moderately in dd, ICR and BALB/c strains, but the DBA/2 strain showed no significant change in the ambulatory activity throughout the repeated 5 times administration of morphine. There was positive correlation between the initial drug sensitivities of animals and the degrees of the reverse tolerance in either methamphetamine or morphine. Furthermore, the reverse tolerance to methamphetamine and morphine was sometimes transferable, although such cross interaction varied among mouse strains.

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A brief brain ischemia produces morphological damage of hippocampal CA1 pyramidal cells without affecting the sensitivities of psychoactive drugs in two types of discrete avoidance tasks in Mongolian gerbils.

Effects of subcutaneous administration of psychoactive drugs: methamphetamine (0.13-1 mg/kg), chlorpromazine (0.5-2 mg/kg), physostigmine (0.05-0.2 mg/kg), scopolamine (0.031-0.5 mg/kg), pentobarbital (5-20 mg/kg), diazepam (0.5-2 mg/kg) and morphine (1.3-5 mg/kg) on discrete lever-press and shuttle avoidance responses were investigated in Mongolian gerbils that had received a brief (5 min) bilateral brain ischemic operation. Although some of the ischemic animals tended to show a retardation of acquisition of the avoidance responses, the established baselines were almost identical between the sham-operated and ischemic groups. In the lever-press task, morphine increased the response rate, whereas chlorpromazine, physostigmine, pentobarbital and diazepam decreased both the response and avoidance rates in a dose-dependent manner. In the shuttle avoidance task, both the response and avoidance rates were dose-dependently increased by methamphetamine, scopolamine and morphine, but chlorpromazine, physostigmine, pentobarbital and diazepam dose-dependently decreased them. These drug effects were almost the same between the sham-operated and ischemic groups. However, the ischemic-operation produced a significant loss of pyramidal cells in the CA1 sector of the hippocampus, the remaining level being less than 10% that of the sham-operated control animals.

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Breeder differences within Wistar strain rats in step-through type passive avoidance response.

Characteristics of acquisition and retention of the one-training and repeated-training passive avoidance responses of the step-through type were investigated in 3 lines of so-called Wistar strain rats: HLA:Wistar, JLA:Wistar and Std:Wistar and in F344/Du Crj rats. In the adaptation and the first acquisition trials in the repeated-training task, Std:Wistar rats took comparatively longer latency times to enter the dark chamber from an illuminated runway than the other lines and strain of rats. In contrast, JLA:Wistar rats took a number of trials to stay for 300 sec or longer in the runway. HLA:Wistar, Std:Wistar and F344/Du Crj rats showed similar response latencies in the first retention trial. JLA:Wistar rats showed the shortest latencies among 3 lines of Wistar and F334/Du Crj rats, exhibiting much poorer acquisition and retention abilities than the other rats. The response latencies in the retention trials were longer in the order of HLA:Wistar greater than or equal to F344/Du Crj greater than Std:Wistar greater than JAL:Wistat rats. These results suggest that there are marked breeder differences in their passive avoidance response even in the rats that have the same strain name.

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[Behavioral study on an antitussive and expectorant, and of its constituents. I. Effects on ambulatory activity and discrete lever-press avoidance response in mice].

Effects of oral administration of a commercial preparation of an antitussive and expectorant (BRON-W Solution, SS Pharmaceut., BRON), and of its constituents; dihydrocodeine (2HCOD), methylephedrine (MEPH), caffeine (CAF) and chloropheniramine (CPA), were behaviorally investigated by means of ambulatory activity and discrete lever-press avoidance response in mice. In 1ml of BRON, 2HCOD 1mg, MEPH 2mg, CAF 2.06mg and CPA 0.4mg are contained with 0.25ml of Senega sirup. BRON 5 and 10ml/kg increased the ambulatory activity in a dose-dependent manner, and suppressed the avoidance response at 10ml/kg. Similar behavioral effects were reproduced by the administration of a mixed solution, in which 2HCOD, MEPH, CAF and CPA were contained at the same doses with those in BRON 10ml/kg. However, such the effects could not be observed after the administration of the drug solutions in which CAF was not contained. The combined administration of 4 drugs at the doses corresponding to 40ml/kg of BRON elicited significant increase in the ambulatory activity and disruption of the avoidance response, eliciting a decrease in the avoidance rate. Though these behavioral effects markedly changed when CAF was eliminated from the solution, an elimination of either 2HCOD, MEPH or CPA was also effective to modify the behavioral effect. Furthermore, combined administration of 4 drugs and MEPH + CAF + CPA at the doses equivalent to those contained in 40ml/kg of BRON produced death of 1 or 2 mice out of 10-14. The present results suggest that the ambulation-increasing and avoidance-suppressing effects of BRON were mainly produced by CAF, and that 2HCOD, MEPH and CPA are also involved therein. In addition, there is a possibility of acute death during BRON-abuse.

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[Behavioral study on an antitussive and expectorant, and of its constituents. II. Effects on ambulatory activity after repeated administration, and a modification of the methamphetamine sensitivity in mice].

Effects of repeated oral administration of a commercial preparation of antitussive and expectorant, BRON-W Solution (SS Pharmaceut., BRON; 10ml/kg), and of single and combination of dihydrocodeine (2HCOD; 10mg/kg), methylephedrine (MEPH; 20mg/kg), caffeine (CAF; 20.6mg/kg) and chloropheniramine (CPA; 4mg/kg) were investigated by means of ambulatory activity in mice. The drug doses tested were identical with those in BRON 10ml/kg. The drug administration was conducted 5 times at intervals of 3-4 days. Furthermore, 4 days after the final treatments, all mice were given methamphetamine 2 mg/kg s.c. In the single administration regimen of individual drugs, only CAF significantly increased the ambulatory activity. However, there was no significant change in the ambulation-increasing effect of CAF after the repeated administration. The other 3 drugs failed to elicit any marked change in the activity throughout the 5 times administration. Such the repeated administration of the individual drugs induced no significant change in the sensitivity to the ambulation-increasing effect of methamphetamine. BRON and BRON-corresponding combination of 4 drugs increased the ambulatory activity in the 1st administration, and the ambulation-increasing effect was progressively enhanced by the repeated administration of these preparations. On the other hand, although CAF-containing solutions significantly increased the ambulatory activity in the 1st administration, the proportions of the changes in the ambulatory activity during the repeated administration regimen were different from that observed after BRON. The combined administration of 2HCOD + MEPH + CPA failed to increase the ambulatory activity in the 1st administration, but significantly increased it in the 2nd and 3rd administration, then elicited again no significant increase in the activity in the 4th and 5th administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Characteristics of circadian rhythm of wheel-running activity and drinking behavior in Mongolian gerbils.

Circadian patterns of wheel-running activity and drinking behavior of Mongolian gerbils were investigated under a 24-h light-dark cycle (LD, 12: 12). Although the circadian pattern of drinking behavior was less clear than that of the wheel-running activity, the two behaviors tended to alter in parallel with each other in 5 out of 10 gerbils. However, the other 5 gerbils exhibited less synchronization between these circadian patterns. Furthermore, there were marked individual differences in the gerbils' circadian patterns, demonstrating not only nocturnal, boundary (showing a peak around the time-of-day of the changing from light period to dark period), and/or diurnal patterns, but also a free-running pattern during the observation period of 79 days. The present result may be due to behavioral characteristics that indicate the gerbils may still be wild type. It is therefore important to know behavioral characteristics of Mongolian gerbils in preclinical evaluation of psychotropic drugs.

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Anticonflict effect of caffeine: investigation by punishment and hypertonic NaCl solution procedures in mice.

Anticonflict effects of caffeine and diazepam were investigated by two procedures in water-deprived mice; punishment procedure in which the water drinking was suppressed by an electric foot shock, and hypertonic NaCl solution procedure in which the mouse was given 2% NaCl solution in place of tap water to suppress the drinking. Single administration of caffeine (1, 3, 10 and 30 mg/kg) and diazepam (0.25, 0.5, 1 and 2 mg/kg), and combined administration of caffeine (10 mg/kg) plus diazepam (1 mg/kg) were conducted. The mouse's drinking behavior was measured for 40 min immediately after each drug administration. Diazepam 0.25 mg/kg in the punishment procedure, and caffeine 30 mg/kg and diazepam 2 mg/kg in the hypertonic NaCl solution procedure were ineffective to significantly disinhibit the suppressed drinking. However, the other doses of caffeine and diazepam significantly disinhibited the suppressed drinking in both procedures. When the combined administration of caffeine and diazepam was carried out, no enhancement of the effect was observed as compared with those of the single administration of the individual drugs. The present results suggest that caffeine possesses an anticonflict effect at certain doses, although it is pharmacologically different from benzodiazepine anxiolytics.

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