Studies on the Therapeutic Effect of Gan-Mai-Dazao-Tang in
Experimental Endogenous Depression Model
英文論文名稱: Studies on the
Therapeutic Effect of Gan-Mai-Dazao-Tang in Experimental Endogenous
Depression Model
指導教授: 林昭庚 ; 謝明村 ; 蕭世朗 指導教授(英文姓名): Lin Jaung-Geng ; Hsieh Ming-Tsuen ;
Shiau Shyh-Lang 學位類別: 博士 校院名稱: 中國醫藥學院 系所名稱: 中國醫學研究所 學號: 8140004 學年度: 84
語文別: 中文 論文頁數: 83 關鍵詞: 內源性憂鬱症 ; 內分泌變化 ; 單胺 ; 甘麥大棗湯 英文關鍵詞: endogenous
depression ; endocrine change ; monoamines ; Gan-Mai-Dazao-Tang
According to the depression animal model proposed by Vogel (1982),
neonatal injection of clomipramine could induce abnormal behaviors
similar to endogenous depression in human.
We used the same animal model to investigate the effects of
Gan-Mai-Dazao- Tang (GMDT) on
hedonic index such as sucrose consumption test (licking volume,
total licking numbers, licks per ml, and licking rate), locomotor
activities and exploratory behaviors measured by opto-varimex known
as dark field test, concentration of serum endocrines such as T3,
T4, TSH, testosterone, prolactin, cortisol, as well as 5-HT , and
brain monoamines including NE, DA, and 5-HT.
Clomipramine (15mg/kg, bid) was injected to Sprague-Dawley
rats of 8 to 21 day-old for the experimental group.
Then at 4 months old:
Group A: Normal control rats received
normal 0.9% saline (1ml/kg,
bid) injection. n=10
The rats were divided into
study 4 groups:
Group B: low dose of GMDT (1.0
g/kg, qd.) n=10
Group C: high dose of GMDT
(2.5 g/kg, qd.) n=10
Group D: amitriptyline
hydrochloride (10 mg/kg, qd.) n=10
Group E: (study control group) 0.9%
saline (1ml/kg, qd., group E, n=10
We measured the body weight, sucrose consumption behaviors (licking
volume, total licking numbers, and licking rate), locomotor
behaviors (stool numbers, freezing time, horizontal, vertical, and
activity counts), serum endocrines ( T3, T4, TSH, testosterone,
prolactin, cortisol, and 5-HT), and brain monoamines (NE, DA, and
5-HT) after the 2-week treatment course. Analysis of Variance was
used to compare the mean values of parameters for five groups.
The results were as follows: Group E was significantly different
from group A in body weight and all variables in sucrose consumption
hehaviors, locomotor activity, serum hormones, and brain monoamines.
B and C groups had significantly increased mean values of body
weight than E group. For sucrose consumption behaviors, B and C
groups showed significant increase of licking volume at 1% sucrose
solution, but only significant increase at 5% of sucrose solution in
group C was observed. The increase in total licking numbers and
licking rate at water, 1% and 5% of sucrose solution in B and C
groups was significantly higher than that in E group. For locomotor
behaviors, B and C groups were significantly different from E group
in stool numbers, freezing time, horizontal and activity acounts.
For serum hormones, significantly increased level of TSH and
serotonin in B and C groups compared to E group was found, Whereas
decreased level of prolactin in C group compared to E group was
found. For monoamines, an increased level of brain NE in B and C
groups compared to E group was observed, while C group showed
significantly higher level of brain DA and 5-HT than E group.
In conclusion, these data support the hypothesis that endogenous
depression has abnormal sucrose consumption behaviors, locomotor
activity, serum TSH, prolactin, cortisol, 5-HT and brain monoamine
levels. GMDT improved the hedonic reactivity, locomotor activities
and exploratory behaviors, abnormal levels of serum TSH, 5-HT,
prolactin, and brain NE, DA, and 5-HT in
endogenous depression rats. The
therapeutic effects of D group was similar to that of C group, but
it existed the over sedation effect.
Note:
Endogenous
depression is a group of symptoms that
resemble depression but are not precipitated by a stressful
experience, especially psychomotor agitation or retardation,
insomnia and early morning awakening, weight loss, excessive guilt,
and a lack of reactivity to one\'s environment. (answers.com)
qd (quaque in die) means
once a day.
b.i.d. (bis in die) means
twice a day.
Compiled and
annotated by:
Joe Hing Kwok Chu
See: http://cancerweb.ncl.ac.uk/cgi-bin/omd?amitriptyline+hydrochloride
Vogel等在1982年提出動物憂鬱模式研究中藥甘麥大棗湯的療效，幼鼠出生第八天就給予皮下注射一種三環抗憂鬱劑
clomipraminehydrochloride連續兩週，四個月大後會產生一些類似人類內源性憂鬱症的異常行為。
實驗組共40隻，隨機分為：
B組，(甘麥大棗湯低劑量組，每天口服
1.0 g/kg 一次， 連續二週)、
C組，(甘麥大棗湯高劑量組，每天口服
2.5g/kg 一次，連續二週)、
D組，(西藥組 ， 每天腹腔注射 amitriptyline
hydrochloride 10 mg/kg 一次，連續二週)、
E組(實驗對照組， 每天腹腔注射 0.9% 生理食鹽水 1ml/kg 一次， 連續二週)四組。
A組另 以10隻幼鼠給予皮下注射 0.9%生理食鹽水作為A組(正常對照組， 每天腹腔注射 1ml/kg 一次， 連續二週)。以
糖耗試驗與紅外線運動量偵測儀(相當於昏暗而封閉的空間試驗)偵測喜好行為與探索能力及自發運動量，並結合血清三碘甲狀腺素(T3)、甲狀腺素
(T4)、甲狀腺刺激素(TSH)、睪固酮(testosterone)、泌乳激素(prolactin)、皮質素醇(cortisol)、血清促進素
(5-hydroxytryptamine,
5-HT)等精神神經內分泌變化，且同步使用高效液相層析儀分析大鼠腦內正腎上腺(norepinephrine , NE
)、多巴胺(dopamine, DA )、血清促進素的含量，以測定甘麥大棗湯治療內源性憂鬱症的療效以及其機轉。
實驗結果顯示(1)E組與A組比較體重減輕，對水及糖水之飲量、總舔次數、舔效及舔速皆降低，排便次數多，不動時間延長，自發運動量減少，且血清
prolactin， cortisol濃度偏高，TSH, 5-HT以及腦內NE, DA,
5-HT濃度偏低；皆達統計上之顯著標準(p<0.05)。(2)C組與E組比較體重顯著增加，不同濃度的糖水飲量、總舔次數與舔速改變，其排便次數減少及不動時間縮短，而自發運動量增加。血清之prolactin濃度趨向正常，並能提高腦內NE,
DA, 5-HT以及血清TSH, 5-HT的濃度。(3)B組除了不同濃度的飲量增加，血清之
prolactin， cortisol 濃度的降低，以及腦內DA,
5-HT濃度的提升方面不如C組外，其餘的統計結果皆與C組相同。(4)D組與E組比較可顯著增加體重，不同濃度的糖水飲量、總舔次數與舔速，而排便次數減少，但不動時間延長及自發運動量下降。可降低血清之cortisol濃度，並能提高腦內NE,
DA以及血清TSH的濃度。
綜合以上結果(1)內源性憂鬱症動物模式顯示生理、行為以及病理的指標；而(2)甘麥大棗湯對內源性憂鬱症大鼠之體重、享樂效應、探索能力、自發運動量，血清TSH,
prolactin, 5-HT以及腦內NE, DA, 5-HT濃度異常皆有改善作用；且(3)此藥方無amitriptyline抗憂鬱劑的過度鎮靜的副作用。