The mechanism of development of experimental gastric ulcers, induced in rats by combined immobilization and electric shock, was analyzed pharmacologically with peripheral neurotropic agents. It is concluded that: (1) The most marked preventive effect in the development of the experimentally induced gastric ulcers was displayed by agents capable of blocking the ascending activation system of the reticular formation. (2) Sympathetic fibers, which disrupt the trophism of the gastric wall, form the efferent portion of the reflex arc. (3) Gastric secretion does not appear to be the primary cause of ulceration

Zabrodin, O. N.

English

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NASA TM-76157
EXPERIMENTAL GASTRIC ULCERS INDUCED BY IMMOBILIZATION AND
ELECTRIC SHOCK OF MATS AND THEIR PHARMACOTHERAPY
O.N. Zabrodin
(NASA-TM-76157) EXPERIMENTAL GASTRIC ULCERS 	 N80-27981
INDUCED BY IMMOBILIZATION AND ELECTRIC SHOCK
or RATS AND THEIR PHAR fACCTHERAPY (National	 UttclasAeronautics and Space Ads.inistration) 
7 QbC G3/51 27956HC A02/91  A 01
Translation of "Eksperimental'nyye yazvy zheludko, vyzvannyye
sochetannoy immobilizatsiyey i elektrizatsiyey krys, i ikh
farmakoterapiya," FarmakoloUiya i Toksikolopiya, Vol. 28,
No. 6 0 1965 9 pp 717-719.
I	 3	
^,.
NATIONAL AERONAUTICS AND SPACE ADMINISTRATION
WASHINGTON, D.C. 20546
	 MAY 1980
.	 r
Ili • .
STANDARD TITLE PAGE
1. Report —	 I L z. Piov.rnmont Accession N.. _	 a. Recipient's Catalog No,NASA— 
4. Title and suwiti• EXPERIMENTAI, GASTRIC ULCERS 	 S . Report Date
INDUCED BY IMMOBILIZATION AND ELECTRIC 	 Maw loan
OF RATS AND THEIR PHARMACOTHERAPY 6. Performing Organisation Code i
7. Author(,) O.N.  Zabrod i n e Pharmacology	 8. Performing Organisation Report No.
Sections Institute of Experimental
Medicine USSR Academy of Medical
	
10. Work Unit No.
W
Sciences, Leningrad
11. Contract at Grant Na.
9. Performing Organisation Name and Address	 NASw-3199
Leo Kanner Associates
	 19. Type of Report and Period Counted
Redwood City, California 94063 Translation
12, Sponsoring Agency Name end Address
National Aeronautics and Space Adminis— u. Sponsoring Agency code
tration, Washington, D.C. 20546 Y'
15. Supplementary Notes
Translation of "Eksperimental'nyye yozvy zheludka, vyzvonnyye
sochetannby immobilizatsiyey i elektrizatsiyey krys, i ikh
formakoterapiya," Farmakologiya i Toksikologiya, Vol. 28,
No. 6, 1965, pp 717-719.
1	 Abstracthe most marked preventive effect in the development of ex-
perimentally induced Gastric ulcers in rats was displayed by
agents capable of blocking the ascending activating system
of the reticular formation. Sympathetic fibers, which dis-
rupt the trophism of the gastric wall, form the efferent
portion of the reflex arc. Gastric secretion does not appear
to be the primary cause of ulceration.
17, Kay Words (Selected by Author(s))	 18. Distribution Statement
Unclassified—Unlimited
19. Security Clossif. (of this report) 	 20. Security Clossif. (of this page) 	 21. No. of Pages	 22. Price
Unclassified
	
Unclassified	 7
NASA•HQ
EXPERIMENTAL GASTRIC ULCERS INDUCED BY IMMOBILIZATION AND
ELECTRIC SHOCK OF RATS AND THEIR PHARMACOTHERAPY
O.N. Zabrodin
Pharmacology Section, Institute of Experimental Medicine,
USSR Academy of Medical Sciences, Leningrad
The goal of this work was the pharmacological analysis of the mech. 717*
anism of development of expo rimental gastric ulcers, induced in rats by
combined immobilization of the animals and electric shock for 3 hours
[7].
We used neuratropic agents, which interrupted the reflex arc in var-
ious parts o` it. The preparations were administered intraperitoneally,
10 min before the start of stimulation with electric current.
It turned out that the number of destructive changes in the stomach
wall in tests with the so called central sedatives phenobarbital and
amobarbital (100 mg/kg) were 6 and 5 times less than in the control, on
the average. Urethane (1 g/kg), chloral hydrate (100 mg/kg) and
paraldehyde (3 g/kg), so called cortical sedatives, in doses which
induced the side position (seminarcosis), even increased the number of
destructive lesions, especially urethane. The central cho-linolytic
diazyl (3 mg/kg), administered twice, decreased the number of destructive
lesions of the stomach mucoso 3.8 times. In tests with aminazine (20
mg/kg), an appreciable preventive effect was observed. The number of
destructive changes in test group animals was decreased 5.3 times, com-
pared with the control group (see figure).
Morphine, administered at a dose of 5 mg/kg, which caused complete
analgesia did not decrease the rate of destructive lesions, but it con-
siderably reduced their severity. In the test with morphine, there were
point erosions of the mucoso without hemorrhage, while distinct ulcerous
defects filled with clotted blood were observed in the control. The
M
umbers in the margin indicate pagination in-the foreign text.
1
;.	 a greatest protective effect was noted with sym-
r	 a
s^	 b	 ^ c patholytin (5 mg/kg), which was administered an
hour before the start of electric shock (see 
figure).	 The s
	
ympatholytio guanethidin• (10
t a mg/kg), which does not block the adrenergic
J a system, also administered an hour before the
ZIP
start of electric shock, had less protective
I
F
F effect:
	 the number of destructive changes in
one control animal was 2.4 but, in the test,
Effect of, gmin- 1.7.	 Atropine did not affect the number of
azine and sym-
patholytin on destructive changes in the stomach.
formation of
gastric ulcers in
rats.	 Column In comparing the results obtained, it was
height designates found that phenobarbital, amobarbital, diazyl
average number of
damaged sections and aminazine had the greatest preventive effect,
in one animal. i.e., those compounds which block the conduct of
Key:
	
a. Control nerve impulses in the ascending activating sys-
b. Aminazine tem of the reticular formations.
	
Meprobamate,
(20 mg/kg)
c. Sympotholytin which excites the ascending activating system of
(5 mg/kg) the reticular formations in the dose we tested
(50 mg/kg) [4], increased the lesion frequency.
In the mechanism of the preventive effect of the central cholinolytic
diazyl, its blocking effect on the m-cholinergic system of the brain-
stem evidently can play a part.
	
Our tests have shown that diazyl had a
pronounced protective effect in the development of experimental gastric
ulcers of rats and, at the some doses, it prevented the onset of
r	 %	 arecoline tremor in them, while difosil and typhen had such a capacity
to a negligible extent and did not protect the stomach mucoso from the
development of destructive changes in it.
Aminazine, which proved to be ineffective for the prevention of
neurogenic dystrophy induced by trauma of the duodenal region, actively
protected the stomach mucosa from destructive lesions in electric shock
and immobilization of the animals.	 This is consistent with the data of
[2, 5].	 The explanation of this difference in protective effect of
aminazine evidently is that, in the generalized irritation induced by
2 nPTr`' 1 r P.a	 IS
? ;. t py
718
v4::::: _. ,,,. , ,
combined immobilization and electric shock, other pathways of the of.,
ferent portion of the reflex,than in the irritation of the duodenal re-
gion are involved. It can be assumed that aminazine, by blocking the
impulses due to stimulation of the exteroceptors, does not have a similar
effect in stimulation of the interoceptors of the duodenal region. The
explanation of the inadequate protective effect of morphine in the devel-
opment of experimental gastric ulcers in rats evidently is that, in the
doses we used, it did not block the ascending activating system of the
reticular formations.
Analysis of the effect of peripheral neurotropic agents permits the
assumption that the efferent portion of the reflex arc, which disrupted
trophism, are the sympathetic fibers. The results of our tests with
sympatholytin, confirmed by data obtained in neurogenic dystrophies
connected with trauma of the duodenal region, indicate this. The block-
ing of the peripheral adrenergic systems by sympatholytin most effective-
ly prevented the development of destructive changes. The sympatholytic
guanethidine had less preventive effect. This probably is explained by
the difference inn the mechanisms of their sympatholytic actions: guan-
ethidine, which, as is known, decreases the catecholamine concentration
in the tissues and organs and decreases the output of the sympathetic
mediator [3], is itself capable of causing gastric ulcers in rats at
large doses, as was shown by D.G. Rozin. Blocking of the peripheral
cholinergic synapses and complete depression of gastric secretions by
atropine, at a dose of 1 mg/kg, did not prevent the development of
destructive lesions. This confirms the fact that the increased gastric
secretions is not the leading factor in the mechanism of development of
experimental gastric ulcers in rats, which was pointed out long ago in
work performed under the supervision of S.V. Anichkov [8]. This has been
confirmed in the work of American authors [5, 1r].
Conclusions
1. In the development of destructive lesions in the stomach mucoso,
the central neurotropic agents which block the conduct of nerve im-
pulses in the ascending activating system of the reticular formations
719
3
•	 x x
had the greatest preventive effect.
2. The efferent portion of the reflex arc, which disrupted
trophism in the stomach wall, are the sympathetic fibers.
3. Increased gastric secretion is not the leading factor in the
mechanism of development of experimental gastric ulcers, induced in
rats by combined immobilization and electric shock,
4#
REFERENCES
1, Brodie, D.A., Gastroenterology 43, 675 (1962).
2. Hanson, H.M. and D.A. Brodie, J. Appl, Physiol. 15 9
 291 (1960).
3. Khaunina, R.A., Farmakol. i toksikol. 2, 239 (1963).
4. Killam, E.K., Pharmacol. Rev. 4, 175 (IV62).
5. Mengny, Rog Am. Jo Dig. Di s, 5, 911 (1960),
39 -Rpzin, D.G., Tezisy dokl. nauchnoy konferentsii. Eksperimental'nyye
I- maries of Reports to-Scat fic Conference, E'xperimental- and
Clinical Basis for the Use of Neurotropic Agents], Leningrad,
1963 9 p. 149.
79 Zabrodin, O.No, Trudy In-to eksperimental i noy meditsiny AMN SSSR
za 1961-1962 gg . LProceedings of nstitu a of Experimental edi-
cine, USSR Academy of Medical Sciences for 1961-19621 0 Moscow,
1963, vol. 7-8, parts 1-3, p. 212.
8. Zavodskaya, I.S., Arch. into Pharmacol. et Therap. 117, 174 (1958).
5


Experimental gastric ulcers induced by immobilization and electric shock of rats and their pharmacotherapy

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