Biomedical subjects

H Kuribara

Publications and source records attributed to H Kuribara.

At least 73 records · Page 4Linked to original sources

PubMed1994

Can posttreatment with the selective dopamine D2 antagonist, YM-09151-2, inhibit induction of methamphetamine sensitization? Evaluation by ambulatory activity in mice.

Effects of YM-09151-2; cis-N-(1-benzyl-2-methyl pyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylaminobenzamide (YM), a potent and selective dopamine D2 antagonist, on sensitization to methamphetamine (MAP) were investigated by means of ambulatory activity in mice. YM (0.003-0.03 mg/kg SC) reduced not only the acute ambulation-increasing effect of MAP (2 mg/kg SC) but also the induction of MAP sensitization when it was simultaneously administered with MAP in the repeated administration at 3-4 day intervals. Moreover, the post 3-h treatment with YM (0.01 and 0.03 mg/kg) following each MAP administration, at which time the acute ambulation-increasing effect of MAP almost disappeared, significantly and dose dependently inhibited the induction of MAP sensitization. The post 24-h treatment with YM did not show such effect. The present results suggest that blockade of the dopamine D2 receptors during postearly period following MAP administration is responsible for protecting the induction of MAP sensitization by means of ambulatory activity in mice.

Animals↗

PubMed1994

Long-continuous observation of the effects of methamphetamine on wheel-running and drinking in mice.

1. Effects of methamphetamine (MAP) on wheel-running and drinking in mice, housed under 12-hr light-dark schedule (light period; 06:00-18:00), were investigated through long-continuous observation. 2. MAP (1, 2 and 4 mg/kg, s.c.) acutely increased the wheel-running and drinking for 2-4 hr in a dose-dependent manner after the administration at 11:00, midpoint of light period. 3. MAP administered at 11:00 sub-acutely suppressed the spontaneous increment during dark period (18:00-06:00) in both the behaviors. 4. Many factors, such as the time-of-day and interval of the administration as well as the dose administered, affected the behavioral suppression induced by MAP. 5. In addition to these findings, the wheel-running and drinking during the light period increased even on the days without MAP administration. 6. These results suggest that MAP have not only acute stimulant and sub-acute depressant effects, but also long-lasting effects.

Animals↗

PubMed1994

Effects of psychotropic drugs on impairment of acquisition of shuttle avoidance produced by pretreatment with pairs of tone signal and shock in mice.

The acquisition of discrete shuttle avoidance of mouse was significantly impaired by presentation of 120 pairs of a tone signal and an unavoidable/unescapable shock at 30 sec intervals for 3 consecutive days prior to the training session. Caffeine (3 and 10 mg/kg s.c.) reduced such an impairment of the avoidance acquisition, whereas diazepam (0.5-2 mg/kg s.c.), imipramine (30 mg/kg i.p.) and chlorpromazine (2 mg/kg s.c.) enhanced it, when these drugs were administered 10 min before each shock-presenting session. Ethanol (0.8-2.4 g/kg p.o.), nicotine (0.1-1 mg/kg s.c.), methamphetamine (0.1-1 mg/kg s.c.) and morphine (1-10 mg/kg s.c.) did not modify the avoidance acquisition. These results indicate that the nature of impairment of the avoidance acquisition caused by this condition is different from learned helplessness, and elicits different responses to psychotropics.

Animals↗

PubMed1994

Interactions of opioids with caffeine: evaluation by ambulatory activity in mice.

Morphine (up to 10 mg kg-1), buprenorphine (up to 0.1 mg kg-1), pentazocine (30 mg kg-1) and caffeine (up to 10 mg kg-1), significantly increased mouse ambulation. The combination of morphine, buprenorphine and pentazocine with caffeine generally enhanced the effect. Dopamine D1- and D2-receptor bockade, depletion of stored dopamine, and inhibition of dopamine synthesis could reduce the ambulation increased by single administration of morphine, buprenorphine and caffeine, and by combined administration of morphine and buprenorphine with caffeine. Although naloxone (0.1-3 mg kg-1) itself did not change mouse ambulation, at 3 mg kg-1, it reduced the effect of caffeine. The repeated administration of morphine (10 mg kg-1) induced a sensitization to the ambulation-increasing effect, and was inhibited by the combination of caffeine (10 mg kg-1) in the repeated administration schedule. The repeated administration of caffeine (10 mg kg-1) with buprenorphine (0.3 mg kg-1) resulted in a decrease in the effect to the level of caffeine alone. The development of cross-sensitization to morphine (10 mg kg-1) by the repeated treatment with buprenorphine (0.3 mg kg-1) was inhibited by caffeine (10 mg kg-1). Our results suggest that the dopaminergic systems are involved in the enhanced interaction of opioids having agonistic action on mu- or sigma-receptors with caffeine. However, it is also considered that, following the repeated administration, caffeine acts to reduce the sensitivity to the ambulation-increasing effect of opioids, probably inducing up-regulation of adenosinergic systems.

Animals↗

PubMed1994

Effects of SUN 8399, a potent and selective 5-HT1A agonist, on conflict behavior and ambulatory activity in mice: comparison with those of buspirone, tandospirone and diazepam.

Behavioral effects of p.o. administration of SUN 8399, a selective 5-HT1A agonist, on the operant behavior under a MULT VI 1.5 min/FR 5-punishment schedule of food reinforcement and on the ambulatory activity were evaluated in mice, and the characteristics were compared with those of other 5-HT1A agonists, buspirone and tandospirone, and the benzodiazepine diazepam. Diazepam (3 and 10 mg/kg) significantly increased the punished response without eliciting any significant change in the non-punished response; i.e., showing anticonflict action. SUN 8399 (3-30 mg/kg) and buspirone (1-10 mg/kg) did not significantly change either the punished or non-punished responses. Tandospirone significantly increased the non-punished response at 10 mg/kg, but significantly decreased both the punished and non-punished responses at 30 mg/kg. The single administration of SUN 8399 (10 mg/kg), buspirone (3 and 30 mg/kg) and tandospirone (10 and 30 mg/kg) significantly increased the ambulatory activity, while diazepam tended to decrease it. The ambulation-increasing effect of methamphetamine (2 mg/kg, s.c.) was reduced by buspirone (10 and 30 mg/kg) and tandospirone (10 and 30 mg/kg), but enhanced by diazepam (3 and 10 mg/kg). Buspirone (30 mg/kg), tandospirone (10 and 30 mg/kg) and diazepam (3 and 10 mg/kg) significantly reduced the ambulation-increasing effect of scopolamine (0.5 mg/kg, s.c.). SUN 8399 (3-100 mg/kg) did not modify the effects of either methamphetamine or scopolamine. The present results suggest that 5-HT1A agonists scarcely show anticonflict action on the Geller-type conflict behavior in mice. However, SUN 8399 possesses different behavioral characteristics from those of the other two 5-HT1A agonists in terms of interactions with methamphetamine and scopolamine.

Animals↗

PubMed1993

Ceruletide, a cholecystokinin-like decapeptide, differentially reduces the stimulant effect of MK-801 and ketamine: evaluation by discrete shuttle avoidance in mice.

The non-competitive NMDA antagonist, MK-801 (dizocilpine: 0.03-0.3 mg/kg i.p.), a dissociative anesthetic, ketamine (1-20 mg/kg s.c.) and a CNS stimulant, methamphetamine (0.1-1 mg/kg s.c.), dose dependently increased the response rate in mice trained to discrete shuttle avoidance. MK-801 (0.1 mg/kg), ketamine (10 mg/kg) and methamphetamine (0.3 mg/kg) were almost equipotent. The cholecystokinin-like decapeptide, ceruletide, 0.1 micrograms/kg s.c., completely attenuated the response-increasing effect of MK-801 (0.1 mg/kg), although at this dose ceruletide alone did not produce any significant change in the avoidance response. Up to 10 micrograms/kg of ceruletide, which itself decreased the response rate, was required to reduce significantly the response-increasing effect of ketamine (10 mg/kg) and methamphetamine (0.3 mg/kg). On the other hand, haloperidol (0.01-0.1 mg/kg s.c.) decreased both the response rate and the % avoidance dose dependently, and inhibited the response-increasing effects of MK-801, ketamine and methamphetamine to almost the same degree. The present results suggest that comparatively lower doses of ceruletide inhibit selectively the stimulant effect of MK-801. Inhibition of dopamine release from the stored site in the nucleus accumbens may be mainly involved in this interaction.

Animals↗

PubMed1993

Effects of haloperidol on the methamphetamine sensitization: assessment by ambulatory activity in mice.

Haloperidol (HPD: 0.0063, 0.025, 0.1 and 0.4 mg/kg, s.c.) reduced dose-dependently the ambulation-increasing effect of methamphetamine (MAP: 2 mg/kg, s.c.) in mice. The repeated administration of MAP elicited a sensitization to its ambulation-increasing effect, and the development of sensitization was inhibited when MAP was administered in combination with HPD in the repeated administration schedule. However, any dose of HPD could not ameliorate the established MAP sensitization. Whereas, the mice experienced the repeated treatment with HPD 0.4 mg/kg showed an increase in the MAP sensitivity. The present results suggest that HPD, at comparatively higher doses, produces a denervation supersensitivity of postsynaptic dopamine receptors, and shows protective action on the development of MAP sensitization. However, it is also suggested that the established MAP sensitization is irreversible even after the treatment with HPD.

Animals↗

PubMed1993

Dopamine antagonists can inhibit methamphetamine sensitization, but not cocaine sensitization, when assessed by ambulatory activity in mice.

The repeated subcutaneous administration of methamphetamine (2 mg kg-1) and cocaine (10 mg kg-1) at 3-4 day intervals induced sensitization to their ambulation-increasing effects in mice. Subcutaneous administration of SCH 23390 (R-(+)-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine; 0.003-0.03 mg kg-1) and YM-09151-2 (cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4- methylaminobenzamide; 0.003-0.03 mg kg-1), the selective dopamine D1 and D2 antagonists, respectively, reduced dose-dependently the acute ambulation-increasing effect of methamphetamine. The development of methamphetamine sensitization was inhibited when it was administered in combination with either SCH 23390 or YM-09151-2 in the repeated administration schedule. Although SCH 23390 (0.01-0.1 mg kg-1) and YM-09151-2 (0.01-0.1 mg kg-1) also reduced the ambulation-increasing effect of cocaine (10 mg kg-1), neither drug inhibited the cocaine sensitization. Mice given cocaine with SCH 23390 (0.03 mg kg-1) or YM-09151-2 (0.03 and 0.1 mg kg-1) showed higher sensitivity than those given cocaine alone. The present results suggest that, although both the dopamine D1 and D2 antagonists reduce the acute stimulant effects of both methamphetamine and cocaine, they are only effective for inhibition of the methamphetamine sensitization. Mechanisms other than the dopaminergic system appear to be involved in the cocaine sensitization.

Animals↗

PubMed1993

The repeated administration of ketamine induces an enhancement of its stimulant action in mice.

The modification of the stimulant and motor-incoordinate actions of ketamine induced by repeated administration was investigated by means of ambulatory activity and rota-rod performance in mice, respectively. Ketamine (12.5, 25 and 50 mg/kg, s.c.) increased the mouse's ambulation in a dose-dependent manner, and the repeated 5-times administration at 3- to 4-day intervals enhanced the increment effect. However, a disruption of the rota-rod performance by ketamine was not modified by the repeated treatment. These results suggest that a reverse tolerance to the stimulant action of ketamine is produced, and that a tolerance to its motor-incoordinate action may not cause the enhancement.

Animals↗

PubMed1993

SCH 23390 equivalently, but YM-09151-2 differentially reduces the stimulant effects of methamphetamine, MK-801 and ketamine: assessment by discrete shuttle avoidance in mice.

The inhibitory actions of the selective dopamine D1-and D2-antagonists SCH 23390 and YM-09151-2, respectively, on the mouse's discrete shuttle avoidance were almost equipotent at doses ranging from 0.01-0.1 mg/kg. SCH 23390 reduced the stimulant action of methamphetamine (0.5 mg/kg), MK-801 (0.1 mg/kg) and ketamine (10 mg/kg) with a similar potency. YM-09151-2 also antagonized the actions of these drugs, with the following order of effectiveness: ketamine > MK-801 > methamphetamine. The present results indicate that methamphetamine, MK-801 and ketamine have different characteristics of CNS stimulant action through dopamine D2-receptors.

Animals↗

PubMed1993

Effect of OM-853, a cerebral metabolic ameliorator, on ambulatory activity and passive and active avoidance responses in mice and Mongolian gerbils.

Behavioral effects of OM-853 were investigated in both mice and Mongolian gerbils. In mice, OM-853 alone produced no marked change in the ambulatory activity, although it tended to lower it at 100 mg/kg, and this drug (5-100 mg/kg, p.o.) reduced the ambulation-increasing effect of scopolamine (0.5 mg/kg, s.c.) in a dose-dependent manner. Moreover, OM-853 (50 and 100 mg/kg, p.o.) prolonged the latency times shortened by scopolamine under the passive avoidance. On the other hand, in the discrete avoidance situation, OM-853 facilitated the acquisition of shuttle avoidance at 10 and 25 mg/kg, p.o. and lever-press avoidance at 25 and 50 mg/kg, p.o. in the pre-training administration schedule, and the former at 25-100 mg/kg, p.o. and the latter at 10 and 25 mg/kg, p.o. in the post-training administration schedule. In gerbils, OM-853 (50 mg/kg, i.p.) ameliorated the learning deficit of the lever-press avoidance response induced by forebrain ischemia. The present results suggest that OM-853 has beneficial actions on some types of learning and memory in normal, scopolamine-treated and ischemic animals. The possible mechanisms involved are discussed.

Animals↗

PubMed1993

Enhancement of the behavioral toxicity induced by combined administration of ethanol with methylxanthines: evaluation by discrete avoidance in mice.

Ethanol, at 1.6 and 3.2 g/kg p.o., disrupted the discrete lever-press and shuttle avoidances in mice, eliciting decrease in the avoidance rate. The response rate was increased by 3.2 g/kg of ethanol in the shuttle avoidance. The single p.o. administration of caffeine 3-30 mg/kg, theophylline 3-100 mg/kg, or theobromine 3-100 mg/kg produced no significant change in both response rate and the avoidance rate in the lever-press avoidance. In the shuttle avoidance, up to 3 mg/kg of caffeine, and 10 and 30 mg/kg of theophylline or theobromine significantly increased the response rate, though there was no significant change in the avoidance rate at any doses of these methylxanthines. Intermediate doses of methylxanthines ameliorated the ethanol (1.6 g/kg)-induced decrease in the avoidance rate with an increase in the response rate, indicating non-specific amelioration of the avoidance rate. The ethanol (3.2 g/kg)-induced decrease in the avoidance rate was enhanced by methylxanthines in a dose-dependent manner. However, in the shuttle avoidance, the response rate was sometimes increased by the combined administration of methylxanthines and ethanol. The present result suggest that, although ethanol and methylxanthines possess CNS depressant and stimulant actions, respectively, methylxanthines do not specifically ameliorate, but rather may worsen, the ethanol-induced avoidance disruption, indicating an enhancement of the behavioral toxicity.

Animals↗

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↗