서 론
, ,
, , ,
,
, , ,
2007 8 16 2007 8 17
2007 9 3
: ,
(Tel : 054-770-2361, Fax : 054-770-2281, E-mail : kjh@dongguk.ac.kr)
甘麥大棗湯 白鼠 影響
백현, 김장현
원 저
The Effects of Gammaekdaejo-tang (Ganmaidazao-tang) on Rats Subjected to Stress by Immobilization
Hyun Baek, Jang-hyun Kim
Dept. of Pediatrics, College of Oriental Medicine, Dongguk University
Objective : This study was conducted in order to find the effects of Gammaekdaejo-tang (Ganmaidazao-tang, GDT) by subjecting rats to immobilization stress, thereby inducing depression, anxiety and acquisition-retention defects.
Method : Rats treated with normal saline, GDT 200mg/kg and GDT 400mg/kg were subjected to stress by immobilization. Afterwards, behavior changes were observed by elevated plus maze test, acquisition test and retention test in the Morris water maze. The results were obtained by immunohistochemically measuring stress hormone (corticosteroid) levels in the blood.
Results and Conclusions :
1. The open arm test in the elevated plus maze showed that compared with the normal group, the time spent decreased in the control group and increased in the GDT 400mg/kg group.
2. The locomotor activity test in the elevated plus maze revealed that the control group showed significant activity decrease compared with the normal group but significant increase in the GDT 400mg/kg group.
3. The acquisition test in the Morris water maze showed that the acquisitive ability of the control group significantly deteriorated on the 3rd and 4th day compared with the normal group, but improved significantly in the GDT 200mg/kg and GDT 400mg/kg groups.
4. The retention test on the 7th day in the Morris water maze revealed that the retentive ability of the control group significantly deteriorated compared with the normal group, but the retentive ability of the GDT 400mg/kg group significantly improved.
5. The blood levels of corticosteroid in the control group increased significantly compared with the normal group but the levels of corticosterone in the blood of the GDT 400mg/kg group significantly decreased.
Key Words : gammaekdaejo-tang (ganmaidazao-tang, GDT), immobilization stress, elevated plus maze (EPM) test, morris water maze (MWM) test, corticosteroid
1).
, 3 (DSM- )
,
3 (DSM- -R)
4 (DSM- )
2).
( )
, ,
8%, 5%
3).
,
.
(irritability)
4),
5).
6) “ ,
, , , ”
, , , ,
7) ,
8,9) 6-8)
.
,
elevated plus maze(EPM) test, Morris water maze(MWM) test
,
corticosterone
.
재료 및 방법
1. 材料 1)
8 200-250g Sprague-Dawley
(( ) , ) .
,
.
.
9 12 , 9
12 .
21°C, 50±5% .
Scientific name amount(g)
Tritici Immatri Semen ( ) 28.0
Glycyrrhizae Radix(roasted) ( ( )) 6.0
Jujubae Fructus ( ) 5.0
Total 39.0
2)
. (Gamma-
ekdaejo-tang, GDT) 7)
1
Table 1 .
2. 方法 1)
10 6
110 3 .
65 rotary
vacuum evaporator 70%
4-5 .
18.0% , .
2) 4 .
(Normal group; N=11)
(Control group; N=10) 200 /
(GDT ; N=11) 400 /
(GDT ; N=10)
10 200 /
, 400 / 30 . 3)
(immobilization stress)
10 2 3
. ,
,
10). disposable rodent rest- raint cone(Havard 52-9586, Havard instrument, USA)
.
4) Elevated plus maze(EPM) 11,12) (1)
EPM
(closed arm),
(open arm). 60cm
.
.
, 5
,
. 30
EPM .
. (2)
EPM ,
.
5) Morris water maze(MWM) 13) (1)
3 1
MWM .
180cm, 50cm
22±2 30cm .
, ,
.
12cm ,
1.5cm . 4
(NE),
(NW), (SE), (SW)
, .
4 7 ,
, (acquisition test)
(2)
4 7
7
,
. 7 (retention test)
. 6) corticosterone
pentobarbital 0.1 / ,
-70 , Cort kit
corticosterone .
3. 통계처리
± ,
window SPSS 8.0
repeated ANOVA , one-
way ANOVA , Tukey
, P 0.05 .
결 과 1. EPM test
1)
Group Mean±S.E.M.(%)
Normal Control GDT GDT
100.0±0.0 74.5±3.5**
82.1±3.9 93.1±4.6+
Normal : non-stressed group, Control : treated with saline and stressed group, GDT : treated with GDT 200mg/kg and stressed group, GDT : treated with GDT 400mg/kg and stressed group
** Significantly different from the normal group(p<0.01) + Significantly different from the control group(p<0.05)
74.5±3.5%
(p<0.01) , GDT
93.1±4.6%
(p<0.05) (Fig. 1, Table 2).
2)
8.3±2.1
14.5±2.3 (p<0.05)
, GDT
13.5±2.4 (p<0.05)
(Fig. 2, Table 3).
2. MWM 검사 1)
MWM 3
110.5±10.4 sec 78.6±18.3 sec
(p<0.05) GDT
86.0±10.2 sec (p<0.05)
.
120 100 80
60 40
Normal 0
20
**
+
Control GDT I GDT II
Time in open arm(%)
Group Mean±S.E.M.(number)
Normal Control GDT GDT
14.5±2.3 8.3±2.1*
11.3±3.2 13.5±2.4+
Normal : non-stressed group, Control : treated with saline and stressed group, GDT : treated with GDT 200mg/kg and stressed group, GDT : treated with GDT 400mg/kg and stressed group
* Significantly different from the normal group(p<0.05) + Significantly different from the control group(p<0.05)
4
92.1±10.4 sec 49.4±11.5 sec
(p<0.01) , GDT
, 61.4±9.3 sec, 60.5±9.7 sec ( p<0.05)
(Fig. 3, Table 4).
2)
15.6±4.3%
30.7±5.6% (p<0.01)
, GDT 28.4±3.6%
(p<0.05) (Fig. 4, Table 5).
3. 혈청 corticosterone 측정
corticosterone
16 14 12 10
Normal 0
20
*
+
Control GDT I GDT II
8 6 4 2
Number of entered arm
Morris water maze acquisition test(Mean±SEM)(sec)
Group Day 1 Day 2 Day 3 Day 4 Day 5 Day 6
Normal 141.0±24.3 100.4±21.5 78.6±18.3 49.4±11.5 43.1±8.1 41.3±5.6 Control 143.5±21.6 111.5±11.5 110.5±10.4* 92.1±10.4** 56.2±9.2 48.5±8.7
GDT 142.7±17.9 118.5±14.5 98.0±11.3 61.4±9.3+ 51.3±8.6 43.1±7.8
GDT 135.6±21.6 119.5±15.2 86.0±10.2+ 60.5±9.7+ 52.3±10.3 35.0±9.3 Normal : non-stressed group, Control : treated with saline and stressed group, GDT : treated with GDT 200mg/kg and stressed group, GDT : treated with GDT 400mg/kg and stressed group
* Significantly different from the normal group(p<0.05)
** Significantly different from the normal group(p<0.01) + Significantly different from the control group(p<0.05)
124.5±8.5 / 61.8±4.5 / (p<0.01)
, GDT 103.2±7.8 /
(p<0.05) ,
GDT 101.5±7.2 /
(p<0.01) (Fig. 5, Table 6).
고 찰
(depressive neurosis)
14).
,
180.0 160.0 140.0 120.0 100.0 80.0 60.0 40.0 20.0
0.0
1 2 3 4 5 6
Time (day)
Latency to platform(sec)
Normal Control GDT I GDT II
Group Mean±S.E.M.(%)
Normal Control GDT GDT
30.7±5.6 15.6±4.3**
24.0±5.2 28.4±3.6+
Normal : non-stressed group, Control : treated with saline and stressed group, GDT : treated with GDT 200mg/kg and stressed group, GDT : treated with GDT 400mg/kg and stressed group
** Significantly different from the normal group(p<0.01) + Significantly different from the control group(p<0.05)
15). DSM-
2 ,
,
, , ,
, , ,
, ,
,
, ,
, 4
,
. ,
, , ,
16).
35 30 25 20
Normal 0
**
+
Control GDT I GDT II
15 10 5
Time in quadrant(%)
Group Mean±S.E.M.( / )
Normal Control GDT GDT
61.8±4.5 124.5±8.5**
103.2±7.8+
101.5±7.2+
Normal : non-stressed group, Control : treated with saline and stressed group, GDT : treated with GDT 200mg/kg and stressed group, GDT : treated with GDT 400mg/kg and stressed group
** Significantly different from the normal group(p<0.01) + Significantly different from the control group(p<0.05)
,
,
,
.
,
14,17-19)
.
, , , ,
. 20)
“ , , , ,
” ,
21) “
”
, 22) “
”
, 22) “
” ,
.
6) “ ”
“
”
, 23)
“
” , 24)
.
25) “ , ,
, , , ,
”, “ , ”
140 120 100 80
Normal 0
**
+
Control GDT I GDT II
60 40 20
Blood level (ug/dL)
+
, , ,
.
14)
, ,
.
6) “ ,
, , , ”
, , , ,
7), , 8,9)
.
, ,
, ,
,
.
, ,
, ,
, 26,27).
,
. , B
28).
, ,
, ,
,
, A,B ,C,K 29).
30)
SD
, 31) ,
Serotonine Melatonine
, 32) niconitic acetylc-
holine receptor [H3]norepinephrine
.
, EPM test, MWM test
,
corticosterone .
Handley Mithani EPM
,
.
,
.
33). EPM
5
,
, .
30
EPM .
, 400 /
. . EPM
,
, 400 /
.
34) EPM
,
. EPM
,
400 /
200 /
.
MWM
35-37)
.
, (spatial reference memory)
38)
. MWM
MWM 3
, 400 /
. 4
, 200 /
400 / .
, 400 /
.
.
corticosterone .
,
corticosterone
corticosterone
,
200 / 400 /
. Glucocorticoid
, corticosterone
corticosterone
.
, corticosterone
,
,
.
결 론
elevated plus maze test, Morris water maze test
,
corticosterone . 1.
74.5±3.5%
, 400 /
93.1±4.6%
. 2.
8.3±2.1 14.5±2.3
,
400 / 13.5±2.4
. 3.
3
400 / 86.0±10.2 sec
. 4
92.1±10.4 sec 49.4±11.5 sec
, 200 /
400 / 61.4±9.3 sec,
60.5±9.7 sec .
4. 7
15.6±4.3% 30.7±5.6%
, 400 /
28.4±3.6%
.
5. ·
corticosterone ,
124.5±8.5 / 61.8±4.5 /
, 200 /
103.2±7.8 /
, 400 /
101.5±7.2 /
참고문헌
1. . . . . 1998:199-
219
2. . , . .
2003;24(2):27-36
3. Garrison C.Z., Addy C.L., Jackson K.I., McKeown R.E., Waller J.L. Major depressive disorder and dysthymia in young adolescence.
Am J Epidemiol 1992;135:792
4. Mitchell J, McCauley E, Burke P, Moss S.J.
Phenomenology of depression in children and adolescents. J Am Acad Child Adolesc Psychiatry. 1988;27:12
5. , .
Paroxetine
, · 1994;5(1):
83-92
6. . . . . 1989:
597
7 . . . . 1998:996
8. . . . .
2000:48,51,52
9. . . . . 1985:338,
479,487
10. McEwen BS, Magarinos AM. Stress and hippocampal plasticity implications for the pathophysiology of affective disorders. Hum Psychopharmacol. 2001;16(S1):S7-S19 11. Lister, R. G. The use of a plus-maze to
measure anxiety in mouse. Psychopharmac- ology(Berl) 1987:92,180-185
12. Dawson, G. R. and Tricklebank, M. D. Use of the elevated plus maze in search for novel anxiolytic agents. Trends Pharmacol. Sci.
1995;16:33-36
13. Pitsikas N, Algeri S. Effect of oxiracetam on scopolamine-induced amnesia in the rat in a spatial learning task. Pharmacol Biochem Behav., 1992;43:949-951
14. , . . .
. 1992:576-577, 608-611
15. . . . . 1990:305
16. . 4
(DSM- ). . . 1995:419-433
17. . . .
. 1991:72-81
18. . . . .
1983:382,439
19. . . . .
1988:734-736
20. . . .
. 1984:402-405.
21. . . . . 1980:
306
22. . . .
. 1981:176,224
23. . . .
. 1983:429
24. . . .
. 1983:106-107
25. . . . .
1988:417-420
26. . . .
. 1999:540-543, 608-609
27. Chen, S.T., Hsu, C.Y., Hogan, E.L., Maricque, H., Balentine, J.D. A model of focal ischemic stroke in the rat ; reproducible extension cortical infarction. Stroke. 1986;17:738-742
28. , , , . .
. . 1994:391-392
29. . . . . 1997:
758-760,857,856
30. , , .
. . 2001;15(4):
590-594
31. , , , . ,
, Serotonine, Melatonine
. . 1999;12(1):
209-229
32. , , , , .
. 1999; 12(2):183-197
33. Handley, S.L. and Mithani, S. Effencts of
a maze-exploration model of 'fear'-motivated behaviour. Naumyn Schmiedebergs Arch Pha- rmacol. 1984:1-5,327
34. , , , . Elevated
plus-maze ,
. . 2001;9:
125-130
35. Arolfo MP, Tinari RJ Ramirez OA. Equivalent performance in the water maze by rats with an inborn high or low learning capacity in a shuttle box paradign. Physiol Behav. 1996;
59(1):209-212
36. Barrow P. Leconte I. The influence of body weight on open field and swimming maze
the rat. England. Lab Anim. 1996;30(1):22-27 37. Gasbarri A, Sulli A, Innocenzi R. Pacitti C,
Brioni JD. Spatial memory impairment induced by lesion of the mesohipocampal doparminergic system in the rat. USA. Neu- rosci. 1996;74(4):1037-1044
38. Beatty WW, Shavalia DA. Rat spatial memory.
USA. Animal Learning and behavior. 1980;
8(4):550-552
39. Sapolskt R.,Krey L., McEwen B., Prolonged glucocorticoid exposure reduces hippocampal neuron number;implications for aging. J Neurosci. 1985;5:1222-1227