Biomedical subjects

H Kuribara

Publications and source records attributed to H Kuribara.

At least 19 recordsLinked to original sources

PubMed1992

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

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

Animals↗

PubMed1992

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

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

Animals↗

PubMed1992

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

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

Analysis of Variance↗

PubMed1992

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

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

Animals↗

PubMed1992

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

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

Alcoholic Intoxication↗

PubMed1992

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

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

Animals↗

PubMed1992

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

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

Animals↗

PubMed1992

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

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

Administration, Oral↗

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↗

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

Behavioral effects of adenosine agonists: evaluation by punishment, discrete shuttle avoidance and activity tests in mice.

Behavioral effects of propentofylline and N6-(L-2-phenylisopropyl)-adenosine (PIA) were evaluated by operant behavior under a punishment situation, discrete shuttle avoidance response and ambulatory activity in mice. Propentofylline (3 mg/kg, s.c.) and PIA (0.01 mg/kg, s.c.) significantly decreased the punished response without producing a significant change in the non-punished response. Propentofylline and PIA reduced the increase in the punished response induced by caffeine (30 mg/kg) and diazepam (1 mg/kg). Propentofylline and PIA also reduced the increase of ambulation induced by caffeine. Furthermore, the single administration of propentofylline and PIA decreased the response rate and/or % avoidance in the discrete shuttle avoidance situation. However, the effective doses of propentofylline and PIA to reduce the ambulation-increasing effect of caffeine and to produce a change in the avoidance behavior were much higher than those effective for eliciting a significant change in the punished response. The present results suggest that there is an intimate interaction between central adenosine and benzodiazepine systems with regards to the change of punished response.

Adenosine↗

PubMed1991

Characteristics of the ambulation-increasing effect of GBR-12909, a selective dopamine uptake inhibitor, in mice.

Behavioral effects of a dopamine uptake inhibitor, GBR-12909 (GBR), were evaluated by ambulatory activity in mice. The single administration of over 10 mg/kg of GBR, i.p. and p.o., significantly increased the ambulatory activity. The repeated administration of GBR, at only 10 mg/kg, produced a reverse tolerance to its ambulation-increasing effect. However, a cross-reverse tolerance was induced between GBR (10 and 20 mg/kg) and methamphetamine (2 mg/kg) in both directions. Furthermore, 5 mg/kg of GBR significantly enhanced the effects of methamphetamine, cocaine, imipramine, morphine, scopolamine and caffeine. R-THBP, a coenzyme of tyrosine hydroxylase, also enhanced the effect of GBR. In contrast, the ambulation-increasing effect of 10 mg/kg of GBR was markedly reduced by haloperidol, chlorpromazine, tetrabenazine, oxypertine, reserpine and alpha-methyl-p-tyrosine. On the other hand, the effect of GBR was only slightly and/or scarcely modified by apomorphine, caerulein, physostigmine, pilocarpine, N6-(L-2-phenylisopropyl)-adenosine and naloxone. The neurochemical experiment in rats, not in mice, revealed that GBR possessed more dominant action on dopaminergic systems than noradrenergic or serotonergic systems. However, the behavioral characteristics of GBR are similar to those of methamphetamine and cocaine, which possess less selective action than GBR on dopaminergic and noradrenergic systems.

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

[Behavioral assessment of neuroleptics (1)--Active avoidance response].

The active avoidance responses in mice and/or rats are suppressed specifically by antipsychotic drugs at the doses which have no marked effect on the general behaviors and the other operant behaviors. In this respect the active avoidance responses have been applied for the preclinical evaluation of antipsychotic drugs. This paper describes accounting points for carrying out the active avoidance test, in particular continuous and discrete avoidance tasks of lever-press and shuttle types in mice and rats. Finally, the typical samples of the avoidance-suppressing effect of antipsychotic drugs (dopamine D2 antagonists) are presented.

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↗