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리튬에 의한 조건적 미각혐오학습과정에서 당질코르티코이드의 혈중농도 증가의 역할 연구

Increase of glucocorticoids is not required for the acquisition, but hinders the extinction, of lithium-induced conditioned taste aversion

초록/요약

Lithium chloride at doses adequate to induce conditioned taste aversion (CTA) causes c-Fos expression in the paraventricular nucleus and increases the plasma level of corticosterone with activation of the hypothalamic–pituitary–adrenal axis. This study was examined to define the role of glucocorticoid in the acquisition and extinction of lithium-induced CTA. In experiment 1, Sprague-Dawley rats received dexamethasone (2mg/kg) or RU 486 (20mg/kg) immediately after 5% sucrose access, and then an intraperitoneal injection of isotonic lithium chloride (12ml/kg) was followed with 30 min interval. Rats had either 1 or 7 days of recovery period before the daily sucrose drinking tests. In experiment 2, rats were conditioned with the sucrose–lithium pairing, and then received dexamethasone or vehicle at 30 min before each drinking test. In experiment 3, adrenalectomized (ADX or ADX + B) rats were subjected to sucrose drinking tests after the sucrose–lithium pairing. Dexamethasone, but not RU486, pretreatment diminished the formation of lithium-induced CTA memory. Dexamethasone prior to each drinking test suppressed sucrose consumption and prolonged the extinction of lithium-induced CTA. Sucrose consumption was significantly suppressed not only in ADX + B rats but also in ADX rats during the first drinking session; however, a significant decrease was found only in ADX rats on the fourth drinking session. These results reveal that glucocorticoid is not a necessary component in the acquisition, but an important player in the extinction, of lithium-induced CTA, and suggest that a pulse increase of glucocorticoid may hinder the extinction memory formation of lithium-induced CTA.

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목차

Ⅰ. INTRODUCTION 1
Ⅱ. MATERIALS AND METHODS 3
A. Animals 3
B. Experiment procedures 4
1. Dexamethasone or RU486 pretreatment on the conditioning day
4
2. Dexamethasone pretreatment during the drinking test 8
3. Lithium-induced CTA in adrenalectomized rats 8
C. Measurement procedures
1 c-Fos immunohistochemistry 10
2. Quantitative analysis 11
D. Statistical analyses ••••••••••••••••••••• 12
Ⅲ. RESULTS 13
A. c-Fos staining in the paraventricular nucleus 13
B. Dexamethasone or RU486 pretreatment on the conditioning day
16
C. Dexamethasone pretreatment during the drinking test 19
D. Lithium-induced CTA in adrenalectomized rats ••••• 22
Ⅳ. DISCUSSION 25
Ⅴ. CONCLUSION 30
REFERENCES 31
국문요약 40

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