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Biomedical subjects

Y Ichimaru

Publications and source records attributed to Y Ichimaru.

At least 55 records · Page 3Linked to original sources

Auto-titration technique using intracranial self-stimulation and effects of antianxiety drugs.

In order to study effects of antianxiety drugs on the threshold of intracranial self-stimulation (ICSS), the auto-titration technique was used in the two lever Skinner box. This procedure consisted of conventional ICSS except the brain stimulation current intensity was decreased after every 20 lever press for ICSS, and the animal could press the another reset lever (at any time) to reset the stimulation current intensity to the preseted level. The current intensity at which the animal pressed the reset lever (reset current) was defined as the threshold of ICSS. Since reset currents that the animals showed were very stable during this experiment, the effects of chlordiazepoxide, diazepam and meprobamate were studied. The reset current was significantly lowered by 5.0 mg/kg chlordiazepoxide, p.o., at 1 hr after administration accompanied by the significant increase of ICSS, and the reset current was significantly lowered by 20.0 mg/kg of chlordiazepoxide. On the other hand, diazepam did not lower the reset current, although a significant increase of ICSS was observed at 1.0 mg/kg, p.o. The reset current was lowered by meprobamate at 100 mg/kg, p.o., accompanied by the increase of ICSS, and a significant increase of ICSS was observed at 200 mg/kg but not accompanied by lowered reset current. From these results, increased susceptibility to the brain stimulation current may be involved in the facilitating effects of chlordiazepoxide and meprobamate on ICSS.

Animals↗

Effects of cholinergic drugs on aversive operant behavior induced by dorsal central gray stimulation in rats.

Involvement of a central cholinergic mechanism in the central aversive operant behavior induced by dorsal central gray (DCG) stimulation was investigated in rats. Each animal was chronically implanted with bipolar electrodes at the DCG and was trained to press a lever to decrease the DCG-stimulation current. Physostigmine (0.1 and 0.2 mg/kg, i.p.) and arecholine (0.5-2.0 mg/kg, i.p.) produced an increase of DCG-stimulation threshold at 0.5-2 hr and 1-4 hr, respectively, after the administration. On the other hand, scopolamine (0.1-0.5 mg/kg, i.p.) and atropine (5 and 10 mg/kg, i.p.) caused a marked decrease of the threshold at 0.5-2 hr after. In addition, an increasing effect of physostigmine on the threshold was decreased by scopolamine. Physostigmine potentiated the increasing effect of chlorimipramine on the stimulation threshold, while scopolamine suppressed it. These results suggest that the operant behavior induced by DCG-stimulation may be related to not only the central serotonergic mechanism but also to the cholinergic mechanism.

Animals↗

Gastric lesions produced by conditioned emotional stimuli in the form of affective communication and effects of benzodiazepines.

Formation of gastric lesions in response to conditioned emotional stimulus (CES) and effects of benzodiazepines were studied in mice. The CES was introduced in the form of affective communication through a communication box. The "senders" were exposed to electric foot shock and the "responders" were able to receive affective cues such as visual, auditory and olfactory from "senders". The "senders" and "responders" exhibited significantly greater gastric lesions than the controls. Diazepam at doses of 2 X 1 - 2 mg/kg (p.o.) and oxazolam at a dose of 2 X 2 mg/kg (p.o.), reduced the formation of gastric lesions of the "responders" induced non-physically by CES. The present results indicate that "responders" showed bodily changes under CES treatment, particularly in the development of gastric lesions, and that gastric lesions produced by CES were protected by diazepam and oxazolam.

Animals↗

Behavioral suppression using intracranial reward and punishment: effects of benzodiazepines.

Rats were chronically implanted with electrodes aimed at the lateral hypothalamus (LH) and the dorsal central gray (DCG) and trained to press a lever that delivered rewarding stimulation of the LH and punishing stimulation of the DCG. In this situation, both diazepam (5-20 mg/kg, PO) and bromazepam (2-10 mg/kg, PO) caused a marked dose-dependent increase of the lever pressing response in the punished period. In addition, the facilitation of lever pressing in unpunished period was also seen in diazepam (5 and 10 mg/kg). These results show that behavioral suppression on lever pressing maintained self-stimulation reward is inducible following DCG stimulation, and that benzodiazepines exhibit an anti-behavioral suppression effect in this situation.

Animals↗

[Effects of gamma-oryzanol on gastric lesions and small intestinal propulsive activity in mice].

Effects of gamma-oryzanol were studied on gastric lesions induced by both conditioned emotional stimuli (CES) and REM sleep deprivations and on the facilitation of small intestinal propulsive activity by CES in mice. The CES were given by the communication box method, and the REM sleep deprivations were performed by a modified flower pot method. The incidence of gastric lesions in responder mice induced by CES was reduced by twice p.o. administrations at 6 hr interval of gamma-oryzanol at 200 and 500 mg/kg, oxazolam at 2 mg/kg and atropine at 1-10 mg/kg. The incidence in sender mice was also reduced by gamma-oryzanol at 200 and 500 mg/kg. In addition, the incidence of gastric lesions induced by REM sleep deprivation was also reduced by single administration of gamma-oryzanol at 100 and 200 mg/kg and oxazolam at 5 mg/kg. The facilitation of small intestinal propulsive activity in responder mice induced by CES was suppressed by gamma-oryzanol at 100 and 200 mg/kg and atropine at 10 mg/kg. These results indicate that gamma-oryzanol has an antiulcerative action on gastric lesions induced by CES and REM sleep deprivation, and it has a suppressive action on the facilitation of intestinal propulsion induced by CES.

Animals↗

[Effect of amantadine on intracranial self-stimulation behavior and cerebral glucose utilization in rats].

Effect of amantadine, an adamantane derivative, was investigated on intracranial self-stimulation behavior and cerebral glucose utilization (CGU) in rats. The experiments were performed on Wistar strain male rats. The low rate responses induced by low current brain stimulation on lateral hypothalamic self-stimulation behavior in a Skinner box were increased by p.o. administration of amantadine at doses of 5 and 10 mg/kg, but were decreased at doses of over 50 mg/kg. Amantadine at doses of 5 and 10 mg/kg, p.o., increased the running speed in run-way performance of animals rewarded with electric stimulation of the medial forebrain bundle in the lateral hypothalamus. On a "conflict" situation induced by combining the hypothalamic self-stimulation with midbrain dorsal central gray stimulation in a Skinner box, amantadine at doses of 5 and 10 mg/kg, p.o. caused an increase of lever pressing in the unpunished period without affecting the punished responses. The CGU measured by [14C] 2-deoxyglucose autoradiography was increased by i.p. administration of 5 mg/kg. In addition, amantadine at a dose of 5 mg/kg, i.p., decreased the high optic density in bilateral habenulae induced by pimozide at 0.75 mg/kg, i.p. These results indicate that amantadine facilitates the intracranial self-stimulation behavior related to a dopaminergic mechanism at low doses, and inhibits the high local CGU of bilateral habenulae induced by pimozide.

Amantadine↗

Methamphetamine mortality to emotional stimuli administered in the form of affective communication.

Methamphetamine induced mortality in physically stressed and non-physically stressed mice was investigated by employing a communication box in which shocked mice communicated their distress to unshocked mice in neighboring boxes. Intraperitoneal administration of methamphetamine 30 mg/kg caused greater mortality in both the shocked "sender" mice and the unshocked "responder" mice than in control when maintained at 27 +/- 1 degree C. Forty-eight hours after injection, the "sender", "responder" and control mice showed mortality of 80, 60 and 10%, respectively. This result indicates that the mortality of methamphetamine may be potentiated not only by physical stress but also by non-physical stress.

Animal Communication↗

Effects of antianxiety and antipsychotic drugs on DRL responding for brain stimulation.

Satiated rats could be trained to give stable rates of responding for rewarding stimulation of the lateral hypothalamus delivered on differential reinforcement of low rate (DRL) schedule requiring 2 to 8 sec interresponse intervals for reinforcement (DRL-2 to 8). The performance on a DRL-8 schedule was tested 30 min after the oral administration of benzodiazepines. Diazepam (5 and 10 mg/kg) and meprobamate (200 mg/kg) caused significant increases in response rates during the first 5 min of a session, but not thereafter. Bromazepam (1 and 5 mg/kg) also caused a significant increase in the rates during the first and second 5 min. On the other hand, chlorpromazine (20 mg/kg) caused no effect in the first 5 min but decrease in second and third 5 min. These results indicate that DRL schedules with a brain stimulation reward provided a useful tool for evaluation of antianxiety drugs. The advantage of the brain stimulation reward over food reward is that the possible effects of the drugs on hunger motivation need not be considered.

Animals↗

Studies of arrhythmias by 24-hour polygraphic recordings: relationship between atrioventricular block and sleep states.

The relationship between AV conduction disturbances and sleep states was investigated using continuous polygraphic recordings for one full night. The results were as follows: (1) In the case of first-degree AV block, the phasic shortening of the PQ interval was observed during rapid eye movement (REM) sleep. (2) In the case of second-degree AV block (Wenckebach type), the conduction ratio increased transiently during REM sleep and significant relationships were observed between the number of nonconducted P waves and the mean heart rate in each sleep stage. (3) In the case of advanced AV block, complete AV block was observed less frequently during REM sleep and the period of falling asleep. Since the reproducibility of these results from night to night has not yet been investigated, additional evaluation is required.

Adolescent↗

The usefulness of Holter monitoring in the evaluation of antiarrhythmic drug efficacy for tachycardia.

Using Holter monitoring tachycardia was found in 145 out of 2058 patients suffering from various underlying diseases. Three thousand seven hundred and forty monitorings were performed. The mean age of patients was 54.5 years with a range of 19 to 83 years. The observed tachycardia was classified into three types: tachycardia with short duration, tachycardia with long duration and tachycardia with complex form. The attacks of tachycardia were more frequently observed during periods of physical activity than during sleeping periods. The relationship of the number of tachycardia with short duration between 24-hour Holter monitorings was examined in order to establish day to day variability of the attacks. The 95% confidence interval about the resultant regression line was calculated and the percent reduction required for the evaluation of drug efficacy to avoid the chances of interference of spontaneous variation was found to be about 44.0, 55.0 and 82% when the total number of attacks during a 24-hour period were 50, 100 and 1,000, respectively. Holter monitoring showed higher positive results as compared to exercise testing for detection of tachycardia. Higher correlation coefficients between numbers of premature ventricular contractions (PVCs) and the plasma concentrations of procainamide or N-acetylprocainamide were observed in 3 or more successive PVCs than in individually occurring PVCs. Using repeated 24-hour Holter monitorings a significant reduction in the number of tachycardia was observed when the therapeutic concentration was reached after the combined or single administration of the drug. These results suggest that repeated Holter monitorings, exercise testing and determination of plasma level of the drug may be useful for the evaluation of antiarrhythmic drug efficacy for tachycardia.

Adult↗

[Pharmacological action of bromazepam suppository].

Differences between the pharmacological effects of bromazepam given by oral and rectal administration were investigated in mice and rats. 1) Bromazepam dose-dependently prolonged the sleeping time induced by thiopental-Na, ethanol and ether by both administration routes. 2) The analgesic action of bromazepam was recognized by the hot-plate method and the algolytic test. In the hot-plate test, analgesic actions of morphine and pentazocine were potentiated by bromazepam in a dose of 0.5 mg/kg by both routes. 3) The muscle relaxant effect of bromazepam administered rectally was more potent than that administered orally in the inclined screen test and the rotarod test. This effect of bromazepam by rectal administration was approximately 2 times as potent as that by oral administration. 4) Bromazepam inhibited the convulsion induced by maximum electric shock, pentylenetetrazol and picrotoxin. In pentylenetetrazol-induced convulsion, the inhibitory effect of bromazepam administered rectally was 2 times as potent as that administered orally. In the other convulsion test, no significant differences between oral and rectal administration could be recognized. 5) Hyperemotionality and muricide (mouse-killing behaviour) of rats with bilateral olfactory bulb ablations (OB rat) were reduced by oral and rectal administrations of bromazepam in a dose-dependent manner. The effects by rectal administration were more potent than that by oral administration. Bromazepam was approximately 20 times as potent as diazepam administered by the same route. Fighting behaviour in mice subjected to footshock was suppressed by rectal administration of bromazepam, and this effect was as same as that by oral administration. 6) The rate of lever pressing response in the lateral hypothalamic self-stimulation test in the Skinner box was markedly increased by rectal administration of 0.2 mg/kg bromazepam. 7) Methamphetamine-induced hyperactivity of mice was significantly suppressed only by bromazepam administered rectally in a dose of 5 mg/kg. 8) The falling effect of bromazepam on body temperature in normal rats was the same in both administration routes and was dose-dependent. From these data, significant differences of the pharmacological effects between oral and rectal administration of bromazepam were recognized in the duration of action and, in part, potencies; and therefore, rectal administration of bromazepam may be a useful dosage form for clinical use.

Administration, Oral↗