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S Tadokoro

Publications and source records attributed to S Tadokoro.

At least 91 records · Page 5Linked to original sources

Interaction between caffeine and methamphetamine by means of ambulatory activity in mice.

Effects of repeated administration of caffeine as well as interaction between caffeine and methamphetamine were investigated by means of ambulatory activity in mice. The single administration of caffeine increased the ambulatory activity at 10 and 30 mg/kg, sc, but scarcely increased at 3 mg/kg and at 100 mg/kg which is a subconvulsive dose. Methamphetamine 2 mg/kg, sc also increased the ambulatory activity. The combined administration of caffeine (1-100 mg/kg) and methamphetamine (2 mg/kg) showed a synergistic action as compared with the effects of the individual drugs. The repeated 5-times administration of caffeine (10, 30, and 100 mg/kg) at intervals of 3-4 days produced neither tolerance nor reverse tolerance to caffeine. The caffeine-experienced mice showed no marked change in the sensitivity to the ambulation-increasing effect of methamphetamine 2 mg/kg. In contrast, the repeated administration of methamphetamine 2 mg/kg induced not only reverse tolerance to methamphetamine itself but also cross reverse tolerance to caffeine (30 mg/kg). Furthermore, the methamphetamine-experienced mice also showed an increased activity after challenge administration of saline. The present results suggest that, although caffeine showed central stimulant effect, the characteristics are different from those of methamphetamine.

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Changes in ambulatory activity and dopamine turnover in streptozotocin-induced diabetic rats.

We have observed the acute effects of streptozotocin (STZ) on ambulatory activity by employing the automatic apparatus for continuous and direct measurement of drinking and ambulation. Ambulatory activity (counts) in the control periods was 298.2 +/- 20.1 in the dark, 35.6 +/- 9.4 in the light, and 343.9 +/- 24.1 over 24 h. After administration of STZ (60 mg/kg, ip), the ambulatory activity gradually decreased [at 3 days: 165.0 +/- 12.3 in the dark (P less than 0.001), 34.0 +/- 10.5 in the light (P = NS), and 199.0 +/- 10.5 over 24 h (P less than 0.001). For determination of statistical significance, values were compared with those at the same time in the control groups. We observed decreased ambulatory activity in STZ-induced diabetic rats during the dark, but not the light, cycle. Moreover, ambulatory activity in STZ-induced diabetic rats gradually decreased, while the blood glucose level rose. Ambulatory activity correlated inversely with blood glucose level (r = -0.76; P less than 0.05). We measured the ratio of dopamine (DA) to 3,4-dihydroxyphenylacetic acid (nanograms per g) in the striatum. The turnover rate of DA was significantly lower in the diabetic rats than in the control group [diabetic, 0.102 +/- 0.003; control, 0.112 +/- 0.001 (mean +/- SE); P less than 0.05]. A negative correlation between the 3,4-dihydroxyphenylacetic acid to DA ratio and blood glucose level was observed (r = -0.693; P less than 0.01). The present study suggests that there are metabolic abnormalities in the striatum dopaminergic neurons of STZ-induced diabetic rats associated with decreased ambulatory activity.

3,4-Dihydroxyphenylacetic Acid↗

[Effects of buflomedil on ambulatory activity and discrete avoidance responses in mice].

Behavioral effects of buflomedil, 4-(1-pyrrolidinyl)-1-(2,4,6-trimethoxyphenyl)-1-butanone hydrochloride, a vasoactive drug, were investigated by means of ambulatory activity and the discrete lever-press and shuttle avoidance responses in mice. Single administration of buflomedil (1,3,10,30 and 100 mg/kg, p.o.) produced no marked change in the ambulatory activity and the discrete lever-press avoidance response. However, the ambulation-increasing effect of methamphetamine (2 mg/kg, s.c.) was suppressed by 30 mg/kg of buflomedil. The avoidance-suppressing effect of chlorpromazine (1 mg/kg, s.c.) was enhanced by 3 approximately 100 mg/kg of buflomedil, but the avoidance-suppressing effect of physostigmine (0.2 mg/kg, s.c.) was not modified by the same doses of buflomedil. On the other hand, the acquisition of the discrete shuttle avoidance response was not affected markedly by buflomedil 3, 10 and 30 mg/kg, p.o.) when the drug was administered immediately before the start of training. The present results suggest that buflomedil shows a central suppressing effect, probably through catecholaminergic neuronal systems, and that the effect is detectable only by the combined administration with typical psychoactive drugs.

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Breeder differences within Wistar strain rats in acquisition of discrete shuttle avoidance response and in sensitivity to chlorpromazine.

Characteristics of acquisition processes of discrete shuttle avoidance response were investigated in 3 lines of Wistar strain rats: HLA:Wistar, JLA:Wistar, Std:Wistar and in F344/Du Crj rats. Std:Wistar and F344/Du Crj rats rapidly acquired the avoidance response, showing an avoidance rate of higher than 90% until the middle stage of the 1st training session in which 120 trials were carried out, and they also maintained a high level of avoidance response in the latter sessions. HLA:Wistar and JLA:Wistar rats, however, exhibited a poorer acquisition of the avoidance response than Std:Wistar and F344/Du Crj rats. These two lines of Wistar rats finally achieved average avoidance rates of around 80% after 5 sessions of training and showed a long-lasting warm-up period in each session. Std:Wistar and F344/Du Crj rats had more resistance than the other two lines to extinction of the acquired avoidance response. Chlorpromazine (2-8 mg/kg, i.p.) suppressed the avoidance response in a dose-dependent manner. The sensitivities to chlorpromazine were higher in the order of JLA:Wistar greater than HLA:Wistar greater than Std:Wistar not equal to F344/Du Crj rats. These results suggest that there are major breeder differences even in the same strain of rats in their behavioral and physiological characteristics. The present results also suggest that Std:Wistar rats show extremely close characteristics with those of F344/Du Crj rats.

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Acquisition process and effects of psychoactive drugs on discrete shuttle avoidance response in Mongolian gerbils (Meriones unguiculatus).

The acquisition process of the discrete shuttle avoidance response and effects of psychoactive drugs on the established avoidance response were examined in Mongolian gerbils. The gerbils acquired the avoidance response very fast and attained an avoidance rate of higher than 90% until the 2nd training session. The established response rate (frequency of shuttles) was about 2.2/min. Methamphetamine, cocaine, scopolamine, atropine and morphine facilitated the avoidance response, eliciting an increase in the response rate. In particular, the effect of morphine was very marked. In contrast, chlorpromazine, haloperidol, pilocarpine, physostigmine, pentobarbital and diazepam suppressed the avoidance response, eliciting a dose-dependent decrease in both the response and avoidance rates. Methamphetamine, cocaine, scopolamine, atropine and morphine increased spontaneous motor activity in the experimental chamber in which neither electric shock nor conditioned stimulus was delivered during the observation period. However, the drug effects were not quantitatively identical with those in the avoidance response. These results suggest that the behavioral characteristics of gerbils are similar to those of mice in the discrete shuttle avoidance situation.

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Time-related facilitation and suppression of drinking by muscarinic anticholinergic drugs in water non-deprived rats.

Effects of tertiary anticholinergic drugs, atropine (1.3, 2.5, 5 and 10 mg/kg, s.c.) and scopolamine (0.13, 0.25, 0.5 and 1 mg/kg, s.c.), and a quaternary anticholinergic drug, methylatropine (1.3, 2.5, 5 and 10 mg/kg, s.c.), on the drinking behavior were investigated in water non-deprived rats that were housed in a 12-hr light-dark situation (light period: 6:00-18:00) with a free access to food. Atropine, 5 mg/kg, and scopolamine, 0.13 and 0.25 mg/kg, administered at 12:00, significantly increased the drinking during the 12:00-18:00 period. Furthermore, lower to medium doses of atropine increased the drinking during the 18:00-6:00 period. In contrast, the drinking did not change during the 12:00-18:00 period, but decreased during the 18:00-6:00 period in a dose-dependent manner after administration of methylatropine at 12:00, whereas the drinking during the 18:00-24:00 period decreased in a dose-dependent manner when both the tertiary and quaternary drugs were administered at 18:00. However, the drinking during the 24:00-6:00 period increased in the rats that were administered atropine at the dose of 5 or 10 mg/kg at 18:00, while the drinking still decreased after methylatropine at the same time. The present results suggest that in water non-deprived rats, central muscarinic cholinergic blockade is effective for both increasing and decreasing drinking behavior, depending on the doses, when the drug is administered, and time span between the drug administration and the behavior observation. It is also suggested that peripheral cholinergic blockade monotonously suppresses the drinking behavior.

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Enhancement of prolactin-secreting effect produced by repeated administration of haloperidol in the avoidance situation and dopamine neurons in rats.

Male Wistar strain rats subcutaneously administered haloperidol at the dose of 0.035 mg/kg at 3-4 days interval, 10 times, in the avoidance situation. Enhancement of the prolactin-secreting effect of haloperidol was observed when it was given in the home cages at the 10th day after termination of the repeated administration. In these animals, 3H-spiperone binding sites in the pituitary significantly increased, while the DOPAC/DA ratio in the hypothalamus significantly decreased. The enhancement phenomenon may be produced by a decrease in the activity of dopamine neurons in the hypothalamus.

3,4-Dihydroxyphenylacetic Acid↗

Facilitating effect of oxiracetam and piracetam on acquisition of discrete two-way shuttle avoidance in normal mice.

Effects of oxiracetam and piracetam on acquisition of the discrete two-way shuttle avoidance response were investigated in normal mice of the dd strain. When oxiracetam or piracetam was administered only once immediately before the training session, the mice showed a greater number of avoidance responses in comparison with the saline-treated control mice, with the maximum effect at 30 mg/kg of oxiracetam and 100 mg/kg of piracetam. These results suggest that oxiracetam and piracetam facilitate the avoidance acquisition in normal mice.

Animals↗

[Differences of behavioral rhythms observed by flat cage and running-wheel cage in female rat].

The ambulatory, wheel-running, and drinking activities were measured in Wistar-Imamichi strain female rats under 12 L:12 D condition (6:00-18:00), using Gundai type ambulo-drinkometer (for simultaneous measurements of ambulation and drinking) and wheel-drinkometer (for simultaneous measurements of wheel-running and drinking) to compare the rhythmicities of each behavioral activity. These apparatuses are able to measure the behavioral activities over a long period, successively and automatically. The circadian patterns of ambulatory activity had two large peaks at 21 or 24:00 and at 6:00 (acrophase). Contrary to the above results, the wheel-running activity exhibited clear mono-peak at 21:00 (acrophase). Thus, apparent differences of the pattern were observed between the two activities. However, ambulatory and wheel-running activities fluctuated showing 4-days rhythmicity, and both activities increased in estrus and proestrus stages, respectively. The circadian rhythms of drinking activities measured by both apparatuses showed almost same patterns with acrophases at 6:00, and 4-days rhythmicities were also observed and were characterized by remarkable decrease of activity in every proestrus stages. From these results, it is concluded that circadian pattern of ambulatory activity is different from that of wheel-running activity, but circadian patterns of drinking activities are stable regardless of different methods of the measurement. The ambulatory, wheel-running and drinking activities reflect the behavioral changes in sexual cycles.

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Behavioral and neurochemical changes produced by postnatal pretreatments with methamphetamine in rats.

Male neonates of Wistar strain rats were given s.c. 1-4 mg/kg/day of methamphetamine (MAP) for 7 successive days from days 6 to 12 after birth. The acquisition processes of the discriminative lever-press avoidance response were investigated from day 60 after birth. Effects of the postnatal pretreatments with MAP on saturation constants for specific bindings of 3H-spiperone (SPP) and 3H-WB4101, respectively, in 8 brain regions were also investigated at 100-120 days after birth. In addition, dopamine, noradrenaline and the levels of their metabolites were measured in the brain. No significant difference was detected in body weight, gross behaviors and avoidance learning between saline- and MAP-pretreated groups. However, effects of MAP and apomorphine on the locomotor activity significantly increased in the MAP-pretreated group. Significant decreases in Bmax and Kd values of 3H-SPP binding sites in the striatum were detected in the MAP-pretreated group, while significant decreases in Bmax values of 3H-WB4101 binding sites in the cortex and hippocampus as well as those in Kd values in the hippocampus were found in the treated group. Dopamine and noradrenaline levels significantly decreased in the MAP-pretreated group, but on the contrary, their metabolites levels significantly increased. These results suggest that postnatal pretreatments with MAP produce long-lasting behavioral changes associated with an impaired development of catecholaminergic neurons in the rat brain after maturity.

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Enhancement of ambulation-increasing effect produced by repeated administration of methamphetamine in rats and neurochemical changes in catecholaminergic neurons.

Male rats of the Wistar strain were repeatedly given methamphetamine (MAP) at 0.5 mg/kg, s.c., 10 times at a fixed interval of 4 days in different environmental situations. The effects of MAP administration on ambulatory activity and neurochemical parameters in the brain were investigated. MAP (0.5 mg/kg) markedly increased ambulatory activity. The ambulation-increasing effect of MAP was progressively enhanced without accompanying stereotyped behaviors when the drug was repeatedly given in the activity cage. The once enhanced effect was considered to be irreversible. In addition, the pretreatment with MAP in the activity cage produced a decrease in the maximum density of 3H-spiperone binding sites in the striatum and that of 3H-WB4101 binding sites in the cortex and hippocampus, with decreases in catecholamine and increases in its metabolites. However, the enhancement of the ambulation-increasing effect of MAP and changes in the binding sites or catecholamine metabolism were scarcely observed when the drug was repeatedly given to the rats in the narrow cage where horizontal ambulation of the animals was strongly impaired. These results suggest that the enhancing effect of MAP is closely related to the environmental situations to which the animals have been exposed to under the drug effect. Moreover, it is indicated that there is a correlation between the enhancement of the ambulation-increasing effect of MAP and changes in the neurochemical parameters. The enhancing effect of MAP is supposed to have been partially caused by changes in cerebral catecholaminergic systems, in particular an increase in catecholamine turnover.

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Strain differences in the reverse tolerance to methamphetamine and changes in catecholaminergic neurons in mice.

The effect of methamphetamine (MAP) on ambulatory activity and neurochemical changes in catecholaminergic neurons in the brain were investigated in dd and C57BL/6 strains of male mice. The mice were given repeatedly MAP at 2 mg/kg, s.c., 10 times at a fixed interval of 4 days. Single MAP markedly increased the ambulatory activity in both strains of mice. The ambulation-increasing effect was progressively enhanced without accompanying stereotyped behaviors when the drug was repeatedly given. The dd mice showed higher susceptibility not only to single MAP but also to the enhancing effect of the drug (reverse tolerance) that the C57BL/6 mice. On the other hand, non-treated dd mice exhibited lower maximum densities of 3H-spiperone binding sites in the striatum and 3H-WB4101 binding sites in the cortex and hippocampus than non-treated C57BL/6 mice. In contrast, the dd mice exhibited higher noradrenaline turnover than the C57BL/6 mice in the brain regions examined. The repeated administration of MAP produced decrease in the densities of both 3H-spiperone and 3H-WB4101 binding sites in the corresponding regions with increase in catecholamine turnover in dd mice. However, the similar changes were observed only in 3H-WB4101 binding sites and noradrenaline turnover in C57BL/6 mice. These results suggest that the ambulation-increasing effect of MAP is positively correlated with catecholamine turnover, while it was correlated negatively with the densities of catecholamine binding sites. Furthermore, the enhancing effect of MAP is supposed to have been partially elicited by changes in brain catecholaminergic systems, in particular an increase in catecholamine turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

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Characteristics of effects of repeated scopolamine administration on ambulatory activity in mice and methamphetamine sensitivity in the scopolamine-experienced mice: comparison among 6 strains.

Effects of scopolamine (0.5 mg/kg, s.c.) on ambulatory activity were investigated in 6 strains of mice (dd, ICR, BALB, C57BL, C3H and DBA). Scopolamine increased ambulatory activity, and the sensitivities were in the order of ICR greater than C3H greater than BALB greater than DBA greater than C57BL greater than dd. This was different from that produced by methamphetamine (2 mg/kg, s.c.) where the order was ICR greater than dd greater than DBA greater than C3H greater than C57BL greater than BALB. A tolerance to the ambulation-increasing effect of scopolamine was progressively produced in dd, ICR, C57BL and DBA strains, but not in BALB and C3H strains, when the drug was administered 5 times at intervals of 3-4 days. The repeated scopolamine treatment elicited a major enhancement of the sensitivity to the ambulation-increasing effect of methamphetamine (2 mg/kg, s.c.) in BALB and C3H strains and a minor enhancement in the C57BL strain, whereas dd, ICR and DBA strains did not exhibit a marked change in the sensitivity to methamphetamine even after the same treatment with scopolamine. These results suggest that the ambulation-increasing effect of scopolamine is different from that of methamphetamine and that the interaction between scopolamine and methamphetamine varies among different strains of mice.

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[Effects of psychotropic drugs by the cumulative-dosing procedure on lever-press and shuttle discrete avoidance responses in mice].

Effects of psychotropic drugs on lever-press and shuttle discrete avoidance responses were investigated by the cumulative-dosing procedure in mice. For cumulative determination, doses of drugs were given 3 times every 1 h within the same session. As a control, the intermittent-dosing procedure in which a single dose was given twice a week was also tested. Cumulative-dosing of chlorpromazine, haloperidol, tetrabenazine, diazepam, and pentobarbital all produced dose-dependent suppression in lever-press and shuttle avoidance responses. Each cumulative dose-effect curve for chlorpromazine and haloperidol in both avoidance responses, and for tetrabenazine and diazepam in lever-press avoidance response was almost identical with that obtained by the intermittent dosing. The cumulative effects of tetrabenazine in shuttle avoidance response and pentobarbital in both avoidance responses were weak. In contrast, diazepam suppressed shuttle avoidance response in the cumulative dosing, but not in the intermittent dosing. Cumulative dosing of methamphetamine and morphine increased response rates without marked changes in avoidance rates in the shuttle avoidance response. Cumulative dosing of methamphetamine was less effective than the intermittent dosing. In contrast, the cumulative dose-effect curve for morphine was almost identical with that obtained by the intermittent dosing. The present results indicate that the cumulative-dosing procedure may be applicable to the drug evaluation in lever-press and shuttle avoidance responses.

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[Behavioral effects of propentofylline (HWA 285) on ambulatory activity, discrete avoidance response and passive avoidance response in mice].

Behavioral effects of propentofylline (HWA 285) were investigated by means of ambulatory activity, discrete lever-press avoidance and step-through type passive avoidance response in mice. Single administration of HWA 285 produced no marked change in the bodily condition and also produced no changes in ambulatory activity at 1.25-20 mg/kg, s.c.; the discrete avoidance response at 2.5-40 mg/kg, s.c.; and the passive avoidance response at 10-30 mg/kg, s.c. However, 5-20 mg/kg of HWA 285 attenuated the ambulation-increasing effect of methamphetamine (2 mg/kg, s.c.) and scopolamine (0.5 mg/kg, s.c.). HWA 285 tended to attenuate the avoidance-suppressing effect of chlorpromazine (2 mg/kg, s.c.) and physostigmine (0.1 mg/kg, s.c.) at 2.5 mg/kg, while it enhanced the effect of chlorpromazine at 10-40 mg/kg. The mice treated with HWA 285 (10-30 mg/kg) at 30 min before or immediately after the acquisition trial did not show a marked change in the passive avoidance response when the retention trial was done 24 hr after the acquisition trial. The treatment with scopolamine (2 mg/kg, s.c.) at 30 min before the acquisition trial suppressed the passive avoidance response, eliciting a marked shortening of the step-through latency and decrease in % of mice to the 300 sec criterion of latency. The effect of scopolamine was attenuated by combined administration of HWA 285 (30 mg/kg) and treatment with HWA 285 (30 mg/kg) after the end of the acquisition trial. The present results suggest that HWA 285 demonstrates complex behavioral effects which vary dependently on the doses and types of behaviors.

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Differences in acquisition of discrete lever-press and shuttle avoidance responses in 6 strains of mice.

Characteristics of the acquisition processes of discrete lever-press and shuttle avoidance responses (intertrial interval = 25 sec, warning duration = 5 sec with an escape contingency, and 1 session = 1 hr training/day) as well as those of the ambulatory activity were investigated in 6 strains of mice (dd, ICR, BALB/c, C57BL/6, C3H/He and DBA/2). In the lever-press avoidance situation, the dd, BALB/c and DBA/2 strains demonstrated a good avoidance response, showing average avoidance rates of higher than 80% within 10-15 sessions of the training. The C3H/He also demonstrated a good avoidance response, though 20 sessions or more of the training were required to attain to the level. The ICR and C57BL/6 strains demonstrated a poorer avoidance response than the other 4 strains, and achieved average avoidance rates of 30-40%. The dd, BALB/c, C3H/He and DBA/2 strains also demonstrated a good shuttle avoidance response when they were trained in an experimental box of 50 cm in width. In contrast, the ICR and C57BL/6 strains demonstrated an extremely poor avoidance response in this situation, showing an average avoidance rate of less than 10%. However, when the dd, ICR and C57BL/6 strains were trained in a shuttle box of 30 cm in width, they rapidly acquired the avoidance response, and the average avoidance rates finally achieved were much higher than those of the mice trained in the shuttle box of 50 cm in width. In particular, the C57BL/6 strain exhibited the best avoidance response among the 3 strains. The ambulatory activity of the C57BL/6 strain was less than those of the other 5 strains.

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