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전격경련(電擊痙攣) 및 향정신성약물이 가토뇌파와 뇌 Catecholamine양에 미치는 영향

Other Titles
 (The) influence of convulsive shock and psychotropic agents on brain catecholamines and electroencephalography in rabbits 
Authors
 황위현 
Issue Date
1968
Description
의학과/박사
Abstract
[한글]

The influence of convulsive therapy and psychotropic agents on brain catecholamines

and electroencephalography in rabbits



Hawang, Wie Hyun

Department of Pharmacology

Yousei University College of Medicine, Seoul, Korea

(Directed by Prof. W.C. Lee and S.S. Hong)



Recent introduction of phenothiazien and rauwolfia lkaloid derivatives in

psychiatry has resulted in great advantage to treat and prevent various mental

disorders. However, the curative mechanism of convulsive therapy as well as the

mode of action of these drugs has not been well established. Brodei(1958) suggested

that the psychosedative activity of chlorpromazine is attributed to the suppression

on the ergotropic division of the brain, whereas that of reserpine to the

stimulation on the trophotropic division.

Since the finding of a relatively large amount of serotonin and catecholamines in

brain, extensive studies (Twarog et al. 1953; Bogdanski, et al. 1956; Brodie et al.

1958) have been reported concerning the physiological significance of these

substances in brain function. Rosenblatt(1960) and Schildkrauft(1964) and others

postulated that the affctive disorder is developed when the catecholamine content

of the brain. Elations conversely may he associated with an excess of catecholamine

in the brain. In addition Brodie(1958) proposed the hypothesis that the central

depressant action of serotonin is responsible for the stimulation of trophotropic

division of brain while catecholamint, in contrast to serotonin, excites the

central nervous system through the activation of ergotropic division.

In and attempt to elucidate the role of catecholamines on the brain function, the

possible relationship between brain catecholamine content and

electroencephalographic changes were examined under various conditions.

Rabbits of both sexes, weighing approximately 2.5kg. in average, were employed in

these experiments. Grass model 7 polygraph and Grass E-1B subdermal electrode were

used in EEG recording. The catecholamine content of the brain were determined by

Aminco-Bowman spectrophotofluorometric procedures described by Shore and

Olin(1958).

Results and Conclusion

1. The electroshock convulsion was produced by the application of two electrodes

on both sides of the head corresponding to the frontal motor areas. THe electrodes

were connected to alternating currents of 80 volts with the duration of three

seconds. Immediately after the cessation of convulsion, the catecholamine content

of brain reduced to almost one half of the normal value and gradually returned to

the level prior to the induction of electric shock convulsion within two hours.

Three hours later, the brain amine level again began to decrease and reached a

maximal depression of 50%. Concomitantly, the electroencephalographic findings

showed that the normal brain waves of these animals were completely displaced by

slow (δ) waves of high amplitude (200μV)during the maximal depletion of brain

cetecholamines.

The (δ)wave disappeared gradually and a normal brain wave with occasional slow

(θ)wave reappeared within two hours. Four hours later, however, the slow (θ)wave

and (δ)wave were followed by the complete displacement of normal brain wave in

accordance with the decrease of brain catecholamines.

2. The clonic convulsion was induced by the administration of

pentylenetetrazole(30mg/kg) into rabbits. The catecholamine content of brain was

rapidly about one half of normal value immediately after the clonic convulsion and

thereafter returned to a lever prior to the administration of pentylenetetrazole

within two hours. The(θ) and (δ)waves were observed one hour after the

convulsion. Two hours later, these waves were replaced by the normal(α)wave as the

catecholamine content returned to a normal level.

3. Rabbits were pretreated with chlorpromazine (25mg/kg). The brain

catecholamines were markedly reduced to a level of 50% of normal valve 30 minutes

later and this decrease was well mainainted until the end three hours. In relation

to the depletion of brain catecholamines, normal (α)wave was displaced by (θ)and

(δ)waves following the treatment of chlorpromazine.

4. The intraperitoneal injection of reserpine(3mg/kg) depleted almost completely

the brain catecholamines of rabbits within 24 hours. At the end of 24 hours after

the injection of reserpine, the electroencephalographic findings showed the

flattened waves with extremely low voltage, indicating the generalized depression

in the brain function.

5. The pretreatment of insulin(400u.) reduced the brain catecholamines rapidly.

The decrease reached to the maximal within thirty minutes and was well maintained

until the animal had fallen into a deep coma at 150min. after the injection of

insulin.

Concomitantly the brain normal waves were displaced by the slow(θ)and (δ)waves

in accordance with the decrease in brain catecholamines.

From the above result, it may be concluded that the depletion of brain

catecholamines played an important role in the depression of brain activity.

[영문]

Recent introduction of phenothiazien and rauwolfia lkaloid derivatives in psychiatry has resulted in great advantage to treat and prevent various mental disorders. However, the curative mechanism of convulsive therapy as well as the mode of action of these drugs has not been well established. Brodei(1958) suggested

that the psychosedative activity of chlorpromazine is attributed to the suppression on the ergotropic division of the brain, whereas that of reserpine to the stimulation on the trophotropic division.

Since the finding of a relatively large amount of serotonin and catecholamines in brain, extensive studies (Twarog et al. 1953; Bogdanski, et al. 1956; Brodie et al. 1958) have been reported concerning the physiological significance of these substances in brain function. Rosenblatt(1960) and Schildkrauft(1964) and others postulated that the affctive disorder is developed when the catecholamine content of the brain. Elations conversely may he associated with an excess of catecholamine in the brain. In addition Brodie(1958) proposed the hypothesis that the central

depressant action of serotonin is responsible for the stimulation of trophotropic division of brain while catecholamint, in contrast to serotonin, excites the central nervous system through the activation of ergotropic division.

In and attempt to elucidate the role of catecholamines on the brain function, the possible relationship between brain catecholamine content and electroencephalographic changes were examined under various conditions.

Rabbits of both sexes, weighing approximately 2.5kg. in average, were employed in these experiments. Grass model 7 polygraph and Grass E-1B subdermal electrode were used in EEG recording. The catecholamine content of the brain were determined by Aminco-Bowman spectrophotofluorometric procedures described by Shore and Olin(1958).

Results and Conclusion

1. The electroshock convulsion was produced by the application of two electrodes on both sides of the head corresponding to the frontal motor areas. THe electrodes were connected to alternating currents of 80 volts with the duration of three seconds. Immediately after the cessation of convulsion, the catecholamine content of brain reduced to almost one half of the normal value and gradually returned to the level prior to the induction of electric shock convulsion within two hours.

Three hours later, the brain amine level again began to decrease and reached a maximal depression of 50%. Concomitantly, the electroencephalographic findings showed that the normal brain waves of these animals were completely displaced by slow (δ) waves of high amplitude (200μV)during the maximal depletion of brain cetecholamines.

The (δ)wave disappeared gradually and a normal brain wave with occasional slow (θ)wave reappeared within two hours. Four hours later, however, the slow (θ)wave and (δ)wave were followed by the complete displacement of normal brain wave in accordance with the decrease of brain catecholamines.

2. The clonic convulsion was induced by the administration of

pentylenetetrazole(30mg/kg) into rabbits. The catecholamine content of brain was rapidly about one half of normal value immediately after the clonic convulsion and thereafter returned to a lever prior to the administration of pentylenetetrazole

within two hours. The(θ) and (δ)waves were observed one hour after the convulsion. Two hours later, these waves were replaced by the normal(α)wave as the catecholamine content returned to a normal level.

3. Rabbits were pretreated with chlorpromazine (25mg/kg). The brain catecholamines were markedly reduced to a level of 50% of normal valve 30 minutes later and this decrease was well mainainted until the end three hours. In relation to the depletion of brain catecholamines, normal (α)wave was displaced by (θ)and (δ)waves following the treatment of chlorpromazine.

4. The intraperitoneal injection of reserpine(3mg/kg) depleted almost completely the brain catecholamines of rabbits within 24 hours. At the end of 24 hours after the injection of reserpine, the electroencephalographic findings showed the flattened waves with extremely low voltage, indicating the generalized depression

in the brain function.

5. The pretreatment of insulin(400u.) reduced the brain catecholamines rapidly. The decrease reached to the maximal within thirty minutes and was well maintained until the animal had fallen into a deep coma at 150min. after the injection of

insulin.

Concomitantly the brain normal waves were displaced by the slow(θ)and (δ)waves in accordance with the decrease in brain catecholamines.

From the above result, it may be concluded that the depletion of brain catecholamines played an important role in the depression of brain activity.
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