An experiment is described which was designed to cause ulcers in rats, but requiring less restraint time than previously used procedures. The method and results are presented

Buchel, L.

Gallaire, D.

English

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NASA TECHNICAL MEMORANDUM
	
NASA TM-76136
REDUCTION OF THE DURATION OF RESTRAINT FOai
THE PRODUCTION OF EXPERIMENTAL ULCERS IN RATS
APPLICATION TO THE STUDY OF PROTECTIVE SUB-
STANCES
L. Buchel and D. Gallaire
(NASA—TM-76136)	 REDUCTION OF THE DURATION 	 N80-21016
OF RESTRAINT FOE THE PRODUCTICN OF
EXPERIMENTAL ULCERS IN RATS: APPLICATION 'IC
THE STUDY OF PROTECTIVE SUBSTANCES (National 	 Unclas
Aeronautics and Space Administration) 7 p	 G3/51 46775
Translation of "Reduction de la duree de la
duree de la contrainte pour la production d'
ulceres experimentaux chez le Rat. Applica-
tion a 1'etude de substances protectrices".
Comptes Rendus des Seances de la Societe de
Biologie et de ses Filiales (France), Vol.
157, I go. 6, 1963, pp 1225-1228.
MICROCOPY RESOLU110N TEST CHART
NA110NAL BURIAU 01 y1AN(ANUS-116iA
NATIONAL AERONAUTICS AND SPACE ADMINISTRATION
WASHINGTON, D.C. 20546
	 PPRIL 1.980
r
REDUCTION OF THE DURATION OF RESTRAINT FOR
THE PRODUCTION OF EXPERIMENTAL ULCERS IN RATS.
APPLICATION TO THE STUDY OF PROTECTIVE SUBSTANCES
L. Buchel and D. Gallaire, presented by Jeanne Levy /1225*
The production of gastric ulcers in rats by means of restraint,
proposed by Rossi, Bonfils and their collaborators since 1956 [1],
has been applied to the study of the protective activity of either
psychotropic substances or cholinolytic substances, although the
mechanism conditioning the appearance of these lesions is not yet
completely elucidated.
The technique generally employed consists of subjecting some
rats to an immobilization lasting 7 to 25 hours, at the conclusion
of which the number of rats presenting ulcers varies from 58 to
100% [2]. A long duration of restraint constitutes an inconveni-
ence in the study of protective substances, notably in the examin-
ation of rapidly eliminated substances. In order to obtain a re-/1226
duction in the restraint time, Hanson and Brodie [3] subjected
young rats to a previous 48 hour fast; under these conditions, 69%
of the animals developed ulcers after 4 hours of restraint.
We studied the experimental conditions which permit reduction
of the duration of restraint to a minimum, yet not prolonging the
fast beyond 24 hours. To this end, we varied the source of the
rats, their age, the time of restraint, in fasting and non-fasting
animals, but keeping the method of immobilization constant. After
preliminary experiments performed on rats of different origins,
we chose Wistar rats, bred at the Gif-sur-Yvette Selection Center,
male, about 50 days old, weighing from 120 to 140 gm. The animals
subjected to fasting were maintained in lots of 10 in cages with
*Numbers in margins indicate foreign pagination.
1
wood shavings on the floor, deprived of food, bu* not of drink
(water).
TABLE I
Number
of
rats
Duration	 Duration
of fast
	 of res-
hours	 traint
hours
I _ _ Ulcerogenic action
Percentage of	 Average
rats developing	 index
ulcers
1. Rats
20
50
35
21
20
2. Rats
without pri(
0
0
0
0
)r fast subject
1
2
4
5
7
ad to restraint.
0
40
29
43
55
subjected ocly to fast.
0
0.7
0.7
0.9
1.4
0.1
0
0.2
20
	
2'-2	 0
	
5
20	 7	 0	 0
20	 24	 0	 10
3. Rats I subjected t¢ fast followed by restraint.
20 24 2 70 1.9
20 24 2 112 85 2.8
39 24 2 112 82 2.8
140 24 2 112 83 2.5
*The maximum number, if the index was 4	 for all the rats afflicted,
would be	 3.4.
(3)	 Ii. Hanson and D. Brodie,	 J.	 Appl. Physiol., 1960,	 vol.	 15
	 P.
291.
1. METHOD OF IMMOBILIZATION - After light ether anesthesia,
the animals are immobilized by means of a flexible wire gauze
pierced with 4 holes for passage of the feet. The feet are tied
together in pairs with a strip of adhesive tape; the wire gauze
is pressed down on the animals' backs, tailored to the circur:ier-
ence of its body, and also secured in the middle with adhesive
tape. The animals are suspended norizontall,y on a stand; thus they
remain immobilized for the dur°,tion of the restraint, the ambient
temperature being maintained at 22°C, and receiving no food or
drink.	 /1227
2
Substance adininistere Dose Number of
mg/kgl rats
Controls
Atropine sulfate
Dihex,yverine
Chlorpromazine
—t--
	
14//01.25 !
	
10
	
25	 40
	
50	 20
	10	 20
	
^20	 20
2. Expression of the results. The animals having been sac-
rificed by decapitation, the stomachs were immediately opened and
examined after a light water rinsing. All the ulcers observed are
located is the glandular portion of the stomach.
Comparative experiments were performed on groups of at least
20 rats. The percentage of ulcerated stomachs has been noted, as
most authors have done. However, Levis and Beersaerts (1960) mea-
sured in addition, the degree of severity of the lesions, by em-
ploying a special gradation. Following their example, we adopted
a system of grading, taking into account the number of ulcers per
animal: 0 - normal stomach; 1 - one ulcer; 2 - two ulcers; 3 -
three ulcers; 4 - four or , more ulcers. For each group of rats,
we calculated an average index.
3. PRODUCTION OF ULCERS. Table 1 summPrizes the results ob-
tained: 1) from rats without prior fast, subjected to a restraint
varying from 1 to 7 hours; 2) from rats subjected only to a fast
of 2 112 to 24 hours; 3) from rats subjected to a 24 hour fast and
to a restraint of 2 or 2 1/2 hours.
It. appears in Table I that: 1) without prior fast, a 2 112
hour restraint is capable of provoking an Irregular percentage of
ulcers which reaches 55% (average index: 1.4) with a restraint of
7 hours; ?) with a prior fast of 24 hours, 2 1/2 hour restraint.
regularly gives rise in "0, 39 and 140 animals to ulcer formation
in 82 to 855 of the rats (average index: 2.5 to 2.8).
TABLE IT.
Pereenta^e averago
of rats	 e- index
veloping P
ullers
20	 < 0.01 0.2
60	 < O.01 1.4
25	 < 0.ol 0.3
45	 < <^ , ^^ 1 0.7
25 0.01 U.5
3
4. PROTECTION FROM ULCERS. We experimented on rats subjected
to a prior 24 hour fast and to a 2 112 hour restraint.
We used two cholinolytics, atropine (sulfate) and dihexyver-
ine (hydrochloride of cyclohexyl-l-cyclohexane carboxylate of pi-
peridino-2-ethyl) and a neuroleptic, chlorpromazine (hydrochloride)
which we administered by the intraperitoneal route, immediately
after immobilization of the animals, or 2 112 hours before their
sacrifice.	 11228
The results obtained are shown in Table II: 1) the dose of
atropine, effective in our experimental conditions, is less than
that (6 mg/kg) determined by Hanson and Brodie (1960) who utilize
a 4 hour restraint prededed by a 48 ;your fast; 2) with dihex,yver-
ine and chlorpromazine, the degree of protection is a function of
the dose utilized. This regularity of results has not been ob-
served by Bonfils et al (1963) with chlorpromazine after restraints
of 7 to 24 hours.
CONCLUSIONS - 1. In young Wistar rats, about 50 Cays old,
a 2 112 hour restraint following a prior 24 hour fast, provokes
ulcers in a constant percentage of animals.
2. We recommend this technique for the study of protective
cholinolytic or pnychotropic substances.
References
1. G. Rossi, S. Bonfils, G. Liefooghe and A. Lambling, C.R. Soo.
Biol., 1956, vol. 150, p. 2124.
2. S. Bonfils, G. Liefooghe, G. Rossi and A. Lambling, C.R. Soc.
Biol., 1957, vol. 151, P. 1149; S. Bonfils et al, CR Soo.
Biol., 1960, vol. 154, p. 924; Bonfils et al, Therapie,
1960, vol. 15, P. 1096 and 19 6 3, vol. 18, h. NO D. Brodie
and H. Hanson, Gastroenterology, 1960, vol. 38, P. 373;
R. Cahen and A. Fessonier, ANN Pharm hr, 1962, vol. 20,
4
P. 704; M. Fontan et al, Lille Medical, 1959, vol. 4,
P. 647; J. LaBarre, Bruxelles Medical, 1961, vol. 41,
pp. 141 and 661; S Levis and J. Bcersaerts, Arch. int.
Pharmacodyn. 1960, vol. 126, P. 359; M. Simler et al, C.R.
Soc. Biol., 1962, vo1. 156, p. 1495.
3. H. M. Hanson et D. A. rodie, J. Appl. 	 Physiol., 1960,
t. 15 9 p. 291.
5


Reduction of the duration of restraint for the production of experimental ulcers in rats: Application to the study of protective substances

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