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S Tadokoro

Publications and source records attributed to S Tadokoro.

At least 127 records · Page 7Linked to original sources
PubMed1984

Circadian variation in the ambulation-increasing effect of apomorphine after repeated administration in mice.

Circadian variation in the ambulation-increasing effect of apomorphine was investigated after repeated administration in mice. The mice housed in a 12 hr light-dark situation (light period; 6:00-18:00) were treated with apomorphine (0.5 mg/kg) or physiological saline vehicle sc at one of 6 times of day (3:30, 7:30, 11:30, 15:30, 19:30 and 23:30). The same treatment was carried out 5 times at intervals of 7 days, and the ambulatory activity was measured for 1 hr after each administration. Repeated administration of apomorphine produced a reverse tolerance (an augmentation in the activity) to the drug. However, the circadian variation in the activity, which was at maximum during the late dark period (administration at 3:30) and at minimum during the late light period (administration at 15:30), was well maintained even after the repeated administration. The circadian variation in the ambulatory activity observed at the 1st administration in the saline-treated control mice, which was at maximum and minimum during the late dark period and mid light period (administration at 11:30), respectively, tended to abolish after the repeated saline administration. The mice that experienced repeated administration of apomorphine exhibited a cross reverse tolerance to methamphetamine (1 mg/kg sc). The cross reverse tolerance occurred throughout the day, and the circadian variation in the effect of methamphetamine, which was similar to that of apomorphine, was also maintained.

Animals↗
PubMed1984

Augmentation of sensitivity to ambulation-increasing effect of apomorphine induced by repeated administration in mice.

Effect of apomorphine on ambulatory activity in mice was investigated after single and repeated administration. The activity was measured by a tilting-type round activity cage of 20 cm in diameter. Single administration of apomorphine at doses of 0.016-0.13 mg/kg sc tended to decrease the ambulatory activity, while doses of 0.5-4 mg/kg sc increased it. Repeated administration of apomorphine (0.5 mg/kg sc) at intervals of 1 hr, 1 day and 7 days induced an augmentation of sensitivity to the ambulation-increasing effect of the drug regardless of the administration intervals. The same treatments of apomorphine (1 mg/kg sc) produced neither augmentation nor tolerance to it. However, the mice exhibited stereotyped behaviors such as sniffing and climbing after the repeated administration, although they hardly exhibited the stereotyped behaviors on the 1st administration. The augmentation of sensitivity, once produced, was well maintained 1 month after cessation of the repeated administration. The augmentation of sensitivity to apomorphine was produced in mice which had repeatedly exposed to both experimental situations in which the ambulation was freely allowed and perfectly restricted, respectivity, during presence of the acute drug effect.

Animals↗
PubMed1984

[Behavioral effects of amantadine on ambulatory activity and drinking in mice and on continuous and discrete avoidance responses in rats].

Effects of amantadine on ambulatory activity in mice and conditioned avoidance responses in rats were investigated. In addition, the change in diurnal drinking rhythm induced by free intake of amantadine solution was also examined in mice. Amantadine (10-40 mg/kg, i.p.) tended to increase the ambulatory activity in mice. Pretreatment with amantadine (10-40 mg/kg, i.p.) at 30 min or 4 hr before augmented the ambulation-increasing effect of apomorphine (0.5 mg/kg, s.c.), but attenuated that of methamphetamine (2 mg/kg, s.c.). When amantadine solution of 0.1 mg/ml or 0.4 mg/ml was freely given to mice for 7 or 21 days, the amount of fluid intake per day decreased slightly, and the daily doses of amantadine intake were estimated to be 15-80 mg/kg/day. However, no marked change in the diurnal pattern of drinking, showing a higher rate during the dark period and a lower rate during the light period, was observed. These mice also demonstrated an increased sensitivity to the ambulation-increasing effect of apomorphine and a decreased sensitivity to that of methamphetamine as compared with the control mice that drank water with no added drugs. Amantadine (10-20 mg/kg, i.p.) did not induce a marked change in the avoidance responses in rats. However, more than 40 mg/kg, i.p. of amantadine suppressed the avoidance responses with a general worsening of bodily condition. Amantadine (10-20 mg/kg, i.p.) did not modify the avoidance-facilitating effects of methamphetamine (0.13-1 mg/kg, s.c.), atropine (1.3-10 mg/kg, s.c.) and scopolamine (0.031-0.13 mg/kg, s.c.), but attenuated the avoidance-suppressing effects of chlorpromazine (0.25-2 mg/kg, s.c.), haloperidol (0.018-0.05 mg/kg, s.c.), tetrabenazine (0.25-1 mg/kg, s.c.), pilocarpine (2-8 mg/kg, s.c.) and physostigmine (0.1-0.4 mg/kg, s.c.) in a dose-dependent manner. The present results suggest that amantadine affects not only the central catecholaminergic neurons but also the other neurons.

Amantadine↗
PubMed1983

Development of tolerance to ambulation-increasing effect of scopolamine dependent on environmental factors in mice.

Effects of repeated administration of scopolamine at 0.5, 2.0 and 8.0 mg/kg s.c. on ambulatory activity in mice were investigated. The drug was administered 5 times at intervals of daily, 3-4 days and weekly. The ambulation-increasing effect of scopolamine progressively decreased when the mice were put into a tilting-type round activity cage of 25 cm in diameter and 13 cm in height during the presence of the acute drug effect. The tolerance, once produced, was maintained even 1 month after the withdrawal. In contrast, development of tolerance to the ambulation-increasing effect of scopolamine could not be found when the mice were put into a glass jar with a 5.5 cm diameter, in which the ambulation was perfectly restricted, after each drug administration. The present results suggest that the tolerance to the ambulation-increasing effect of scopolamine induced by repeated administration may be elicited by an interaction between the experimental situation and the drug effect.

Amphetamine↗
PubMed1983

Comparison of susceptibilities to the effects of antipsychotic drugs on lever-press avoidance responses between mice and rats.

Effects of antipsychotic drugs, chlorpromazine, haloperidol and tetrabenazine, on lever-press avoidance responses under Sidman avoidance (response-shock interval = 30 sec and shock-shock interval = 5 sec) and discriminated avoidance (intertrial interval = 25 sec and warning duration = 5 sec) situations in male mice of the dd strain were investigated. The results were compared with those in male rats of the Wistar strain. All the drugs tested were administered s.c., and the avoidance responses of the mice and rats were observed for 1 hr after each administration. Chlorpromazine, haloperidol and tetrabenazine suppressed the avoidance responses of the mice and rats in a dose-dependent manner. The susceptibilities of the mice to these drugs were calculated to be 1/5-1/6 as low as those of the rats. However, the potencies of the avoidance-suppressing effects of chlorpromazine, haloperidol and tetrabenazine were estimated to be 1:20:1.3 and 1:18:1.4 by the Sidman avoidance responses in the mice and rats, respectively, and 1:18:1.1 by the discriminated avoidance responses in both the mice and rats. These results suggest that the conditioned lever-press avoidance responses in mice, as well as those in rats, are applicable for the evaluation of antipsychotic drugs.

Animals↗
PubMed1983

Circadian variation in susceptibility to the ambulation-increasing effect of scopolamine in mice.

Circadian variation in susceptibility to the ambulation-increasing effect of scopolamine in mice was investigated. The mice housed under a 12-hr light-dark situation (light period: 6:00-18:00 and dark period: 18:00-6:00) for 5 weeks were administered scopolamine HBr at 0.5 or 2 mg/kg s.c. at one of six times of the day (3:00, 7:00, 11:00, 15:00, 19:00 and 23:00), and the ambulatory activity was measured for 2 hr. Scopolamine induced a dose-dependent increase in the ambulatory activity. In addition, there was a clear circadian variation in the susceptibility to the ambulation-increasing effect of scopolamine. The highest and the lowest overall activity counts during the 2 hr observation period were found when the drug was administered at 3:00 and 15:00, respectively. The present results suggest that the susceptibility to scopolamine in mice is dependent on the time-of-day at which the drug is administered. The reasons which may induce this circadian variation in susceptibility to scopolamine are discussed.

Animals↗
PubMed1983

Effect alteration of methamphetamine by amino acids or their salts on ambulatory activity in mice.

Effect alterations of methamphetamine by pretreatment of amino acids or their salts on ambulatory activity in mice were investigated to confirm a fact that certain amino acids, particularly monosodium L-glutamate, are added to methamphetamine by the street users, and that the amino acids augment the effect of methamphetamine. The ambulatory activity of mouse was measured by a tilting-type round activity cage of 25 cm in diameter. The amino acids or their salts tested were monosodium L-glutamate, monosodium L-aspartate, gamma-amino-butyric acid, L-alanine, L-lysine hydrochloride and L-arginine hydrochloride. A single administration of each chemical at doses of 1 and 2 g/kg i.p. did not induce a marked change in the ambulatory activity in mice. Methamphetamine 2 mg/kg s.c. induced an increase in the ambulatory activity with a peak at 40 min after the administration, and the increased ambulatory activity persisted for 3 hr. The ambulation-increasing effect of methamphetamine was augmented by the pretreatment of monosodium L-glutamate and monosodium L-aspartate at 30 min before the methamphetamine administration, while attenuated by the pretreatment of L-lysine hydrochloride and L-arginine hydrochloride in a dose-dependent manner. Gamma-aminobutyric acid and L-alanine did not affect the effect of methamphetamine. Similar augmentation and attenuation in the ambulation-increasing effect of methamphetamine were induced by the pretreatment of sodium bicarbonate 0.9 g/kg i.p. (urinary alkalizer) and ammonium chloride 0.07 g/kg i.p. (urinary acidifier), respectively. The urinary pH level was elevated by the administration of monosodium L-glutamate, monosodium L-aspartate and sodium bicarbonate, and decreased by L-lysine hydrochloride, L-arginine hydrochloride and ammonium chloride. Gamma-aminobutyric acid and L-alanine did not elicit a marked change in the urinary pH level. The present experiment confirms the fact in human that monosodium L-glutamate augments the effect of methamphetamine. Moreover, the present results suggest that monosodium salts of acidic amino acids augment, and conversely monohydrochloric salts of basic amino acids attenuate the effect of methamphetamine. The alterations of the ambulation-increasing effect of methamphetamine may be due to the urinary excretion rates of the drug through changes in the urinary pH level after the administration of amino acids or their salts.

Amino Acids↗
PubMed1983

[Characteristics of reverse tolerance to ambulation-increasing effect of methylphenidate after repeated administration in mice].

Effects of repeated administration of methylphenidate (MPD) 2, 4, 8 and 16 mg/kg, sc on ambulatory activity in adult male mice of old strain were studied. The ambulatory activity of each mouse was measured by a tilting-type activity cage for 90-150 min after the drug administration. The repeated administration of MPD 2 and 4 mg/kg at intervals of 3-4 days, and 4 mg/kg at intervals of 7 days produced an augmentation in the sensitivity of the mice, i.e., a reverse tolerance, to the ambulation-increasing effect of the drug. However, the repeated administration of MPD 4 mg/kg at intervals of 1 day, and 8 and 16 mg/kg at intervals of 3-4 days did not produce the reverse tolerance to it. The mice repeatedly given 16 mg/kg at intervals of 3-4 days exhibited an augmentation in stereotyped behaviors. The reverse tolerance, once produced, was well maintained 45 days after cessation of the repeated administration. Only a little reverse tolerance to MPD was produced in the mice repeatedly given the drug in their home cage, in which the mice were group-housed, and the extent was significantly less than that observed in the mice given the drug in the activity cage. In addition, the mice showing the reverse tolerance to MPD demonstrated an increase in sensitivity to methamphetamine as compared with the saline-given control mice. The present results suggest that the characteristics of reverse tolerance to the ambulation-increasing effect of MPD is almost identical with that after methamphetamine.

Amphetamine↗
PubMed1983

Differences in cholinergic agonist- and cholinergic antagonist-induced changes in avoidance responses between dd mice and Wistar rats.

Effects of pilocarpine (PILO), physostigmine (PHYSO), atropine (AT) and scopolamine (SCOP) on continuous (response-shock interval = 30 sec and shock-shock interval = 5 sec) and discrete (intertrial interval = 25 sec and warning duration = 5 sec) lever-press avoidance responses in dd strain mice and Wistar strain rats were investigated. PILO and PHYSO suppressed continuous and discrete avoidance responses in both the mice and rats. However, the mice tended to show more sensitivity than the rats to the avoidance-suppressing effect of PILO and PHYSO. AT and SCOP suppressed the avoidance responses in the mice, but facilitated them in the rats. These results suggest that the neural activities of the central muscarinic-cholinergic systems are different between dd mice and Wistar rats.

Animals↗
PubMed1982

Changes in schedule-controlled response and schedule-induced drinking after cholinergic blockers in rats.

The effects of the tertiary cholinergic blockers atropine sulfate (AT) and scopolamine hydrobromide (SCOP), and the quaternary cholinergic blockers atropine methylnitrate (AT-Mt) and scopolamine butylbromide (SCOP-Bt), on operant response (lever-pressing) and adjunctive drinking in the rat developed under a fixed interval (FI) 1.5 min food reinforcement situation were investigated. The tertiary compounds, particularly SCOP, increased total responses, and produced a dose-related decrease in the index of curvature (IC) for local rates of response during the FI. The quaternary compounds, however, did not produce changes in the total responses and the IC for local rates of response. AT, AT-Mt and SCOP suppressed adjunctive drinking, while SCOP-Bt did not. AT and SCOP, but not AT-Mt and SCOP-Bt, decreased the IC for local rates of drinking. AT-Mt suppressed drinking at a uniform rate throughout the FI. In addition, several doses of AT and SCOP tended to increase licking counts at the drinking spout per 1 ml water intake. The present results suggest that central cholinergic blockade increases the response and suppress adjunctive drinking, and that the peripheral cholinergic blockade suppresses only adjunctive drinking. Moreover, central cholinergic blockade may produce changes in the patterns of response and drinking during the FI, and in the manner of drinking at the drinking spout.

Animals↗
PubMed1982

Circadian variation in methamphetamine- and apomorphine-induced increase in ambulatory activity in mice.

The existence of circadian variation in methamphetamine- and apomorphine-induced change in ambulatory activity in mice was investigated. Adult male mice of dd strain, which had been housed on a 12 hr light-dark schedule (light period; 6:00-18:00) for 4 weeks, received injections of either methamphetamine HCl 1 or 2 mg/kg SC at one of six times of day (3:00, 7:00, 11:00, 15:00, 19:00 and 23:00), or apomorphine HCl 0.5 or 1 mg/kg SC at one of six times of day (3:30, 7:30, 11:30, 15:30, 19:30 and 23:30). The control animals were administered a physiological saline vehicle alone at the corresponding times of day. The ambulatory activity of each mouse was measured by a tilting-type activity cage for 3 hr after methamphetamine, and for 1 hr after apomorphine. A circadian variation in the ambulatory activity was observed after the administration of the saline, methamphetamine and apomorphine. Here, the highest activity counts were found when the saline, methamphetamine and apomorphine were administered during the late dark period (3:00 or 3:30), while the lowest activity counts were found when the saline and apomorphine 1 mg/kg were administered during the mid light period (11:00 or 11:30), and methamphetamine 1 and 2 mg/kg and apomorphine 1 mg/kg were administered during the late light period (15:00 or 15:30). The circadian variation in methamphetamine-induced increase in the activity was abolished by a pretreatment with reserpine 2 mg/kg SC 4 hr before, but that of apomorphine was maintained even by the pretreatment with reserpine. The present results suggest that the methamphetamine- and apomorphine-induced increase in the ambulatory activity in mice is dependent on the time-of-day of the drug administration, and the occurrence is mainly due to a circadian variation in activity of the catecholaminergic systems in the brain.

Animals↗
PubMed1982

Enhancement of avoidance-suppressing effect after repeated administration of haloperidol and serum haloperidol in rats.

Adult male rats of the Wistar strain, which were trained under a discriminated lever-press avoidance schedule (intertrial interval; 25 sec. presentation of conditioned stimuli; 5 sec), were given SC 0.025-0.05 mg/kg of haloperidol at fixed intervals of 1, 3-4 and 7 days. The avoidance-suppressing effect of haloperidol was enhanced in parallel to the number of drug administrations until it attained a maximum level. The intensity of the maximum effect tended to be stronger, and the number of administrations necessary to attain it was smaller, when a higher dose was given. When the administration interval exceeded one day, the enhanced effect remained irreversible one month after withdrawal of drug administration. The enhancement of the effect was produced after repeated administrations in an experimental chamber, but not in a home cage. Temporal changes in serum haloperidol concentration were determined 30-90 min after 0.035 mg/kg given SC to the haloperidol-pretreated and saline-pretreated groups. No significant difference in the pharmacokinetic change was detected between the two groups. These results suggest that learning during the drug effect under repeated exposure to a fixed experimental situation influences the enhancing effect.

Animals↗
PubMed1982

An anticonflict effect of gamma-1-glutamyltaurine (Litoralon) in rats.

Effects of gamma-1-glutamyltaurine (GT: Litoralon; Chinoin, Hungary) on rat's operant responses maintained under two types of negative reinforcement (avoidance) schedules: Sidman-type and discriminated avoidances and two types of positive reinforcement schedules and/or conflict schedules: differential water reinforcement of low rate (DRL 20 sec) and multiple fixed ratio 15/fixed ratio 15-punishment (MULT FR 15/FR 15-punishment) schedules were investigated to assess the central effects of GT. GT at 0.1-10 mg/kg i.p. induced no change in either the avoidance or DRL 20 sec responses. However, GT induced a prominent increase in the punished response (anticonflict effect) without eliciting a marked change in the non-punished response on the MULT FR 15/FR 15-punishment schedule. This behavioral change appeared not immediately, but gradually, when doses of more than 1 mg/kg were given; and a maximum level was achieved on days 3-6 and persisted for 7-14 days after the administration. The anticonflict effect of GT was synergistic with that of diazepam, a prototype antianxiety drug. No marked change in gross behavior was observed after GT. The present results suggest a possibility that GT has a central effect which correlates to the anticonflict effect.

Animals↗
PubMed1981

Enhancement of the avoidance-suppressing effects of neuroleptic agents after repeated administration: changes in the discriminated avoidance response in rats.

Changes in the discriminated avoidance response of the rat after repeated administration of N-(1-benzyl-3-pyrrolidinyl)-5-chloro-2-methoxy-4-methylaminobenzamide (YM-08050; 0.01 mg/kg SC) and N-(1-benzyl-3-pyrrolidinyl)-5-chloro-methoxy-4-dimethylaminobenzamide (YM-08051; 0.1 mag/kg SC), potent neuroleptic agents of the benzamide derivative type, were investigated. The avoidance-suppressing effects of YM-08050 and YM-08051, i.e., decreases in the response (lever-pressing) and avoidance rates, were enhanced after repeated administration. The changes in behavior were more marked in animals exposed to the avoidance situation during the period of the drug effect than those given the drugs after the termination of each avoidance session. The enhancing effect, once it had appeared, remained even after 1 week. The present results suggest that the avoidance-suppressing effects of YM-08050 and YM-08051 are enhanced after repeated administration, and that the effect is strongly dependent on the drug experience of the experimental animals and on the experimental situation to which the animals are exposed during the period of the drug effect.

Animals↗
PubMed1981

Correlation between antiavoidance activities of antipsychotic drugs in rats and daily clinical doses.

Effects of oral antipsychotic drugs, 12 phenothiazines, 3 thioxanthenes, 5 butyrophenones and 8 other derivatives on Sidman and discriminated avoidance responses in rats were investigated and compared to their clinical doses routinely used PO. Almost all drugs except sulpiride and clozapine suppressed the avoidance responses with a dose-dependent decrease in the response rate (lever-pressing) and increase in the shock rate in the Sidman avoidance performance or a decrease in both the response and avoidance rates in the discriminated one. Sulpiride (80-640 mg/kg) produced no marked change in the avoidance responses. Clozapine (2.5-10 mg/kg) increased the shock rate or decreased the avoidance rate without eliciting any change in the response rate. The avoidance-suppressing activities of the antipsychotic drugs were well correlated with their clinical daily doses. However, the avoidance-suppressing effects of carpipramine, clocapramine, thiothixene and sulpiride were relatively less potent, while that of clotiapine was more potent than in the clinical activities. The potencies of the avoidance-suppressing effects of each drug on the Sidman and the discriminated avoidance responses were almost identical except for triflupromazine, pimozide, thioridazine, spiclomazine and propericiazine. The former two drugs suppressed the Sidman avoidance response more than the discriminated avoidance response. However, the latter three drugs suppressed the discriminated avoidance response more markedly than the Sidman avoidance response. The present results suggest that the avoidance response in rats is applicable in evaluating the clinical efficacies of antipsychotic drugs.

Animals↗
PubMed1981

[Variability in the effects of psychotic drugs on conditioned avoidance reactions in rats due to warning stimuli].

Different effects of methamphetamine (0.25-1 mg/kg, sc), chlorpromazine (0.5-2 mg/kg, sc), haloperidol (0.25-0.1 mg/kg, sc), diazepam (1-4 mg/kg, sc) and pentobarbital (5-20 mg/kg, sc) on Sidman avoidance response were investigated according to absence or presence of stimulus control. Thirteen adult male rats of Wistar strain were divided into two groups of 6 and 7 each, and trained under Sidman avoidance schedule (WS-group) and the same schedule associated with a 5 sec warning stimulus presentation (buzzer and light) (WS+group). There was no difference in the effect of methamphetamine between the two groups. The avoidance response was inhibited in dose-dependent manner regardless of the stimulus control after chlorpromazine and haloperidol. However, more marked inhibition was always observed in WS-group than in WS+group. Diazepam and pentobarbital also inhibited the avoidance response in WS-group when ataxia-producing doses were given, while no significant inhibition was observed after the same doses of the drugs in WS+group. Thus, the avoidance response without stimulus control was more susceptible to the drugs than that with stimulus control. The present results suggest that Sidman avoidance response is reliable to evaluate psychotropic drugs in screening test.

Animals↗
PubMed1981

[Effects of cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylaminobenzamide (YM-09151-2) on operant avoidance responses in rats (author's transl)].

Effects of cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylaminobenzamide (YM-09151-2), a newly synthesized psychotropic agent, on avoidance responses in rats under a Sidman-type avoidance situation (R - 3 = 30 sec, S - S = 5 sec) and discriminated-type avoidance situation (ITI = 25 sec, CS duration = 5 sec) were investigated. The results were compared with the findings obtained in the case of YM-08050, YM-08051 and sulpiride, benzamide derivatives having similar chemical structures as YM-09151-2, and with the effects of chlorpromazine and haloperidol. After administration of YM-09151-2 (0.0025 - 0.01 mg/kg s.c. or 0.2 - 1.6 mg/kg p.o.), we observed a dose-related suppression of the avoidance responses, which attained to the maximum at 2 - 3 hr and persisted for about 24 hr. The average avoidance-suppressing and anti-amphetamine effects during the 2 hr session were in the order of YM-09151-2, YM-08050, haloperidol, YM-08051, chlorpromazine and sulpiride, when these agents were given s.c. Here, the avoidance-suppressing effects of YM-09151-2 were estimated to be 94-137 times as potent as those of chlorpromazine, and 4-37 times as those of haloperidol. After p.o. administration, the suppressing effects on the Sidman-type avoidance response were in the order of YM-08050, YM-08051, haloperidol, YM-09151-2, chlorpromazine and sulpiride, and on the discriminated-type one in the order of YM-08050, YM-09151-2, haloperidol, YM-08051, chlorpromazine and sulpiride. The present results suggest that YM-09151-2 has a more potent avoidance-suppressing effect when it is administered s.c., while the effect is as potent as that of haloperidol when given p.o. The effect appears rapidly and persists for about 24 hr after either s.c. or p.o. administration.

Animals↗