The frequency and gravity of restraint ulcers were found to significantly diminish in rats previously exposed to brief periods of immobilization. The rats' becoming habituated to restraint conditions probably explains this phenomenon

Lambert, R.

Martin, F.

Martin, M. S.

English

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NASA TECHNICAL XsMORANDUM
NASA TM-76072
EFFECT OF HABITUATION ON THE SUS CEPTIBILITY OF THE RAT
TO RESTRAINT ULCERS
M.S. Martin, F. Martin and R. Lambert
Translation of "Effet de 1
'habituation sur la sensibilite du Rat a1'ulc're de co
nstrainte", Comptes Rendus des Seances de la Societede Biologie et de ses Filiales, Vol. 164, No. 4, 1970, pp 826-828
(NASA—TIC- 76072)
 EFFECT OF HABITUATION ON
THk' SUSCEPTIBILITY OF THE RAT TO RESTRAINT
UIL,.'RS (National Aeronautics a:ud Space
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NATIONAL AERONAUTICS AND SPACE ADMINISTRATIONWASHINGTON, D.C. 20546
	 MARCH, 1980
EFFECT OF HABITUATION ON THE SUSCEPTIBILITY OF THE RAT
TO RESTRAINT ULCERS
M.S. Martin, F. Martin and R. Lambert
Unite de Recherces de Physiopathologie Digestive, INSERM,
H$pital Edouard Herriot, Lyon
When a rat is subjected to repeated periods of restraint, two
opposing factors intervene in the development of gastric lesions:
the cumulative effect of the restraint tends to aggravate these
lesions, and habituation to stress tends to minimize them (1) . We
attem-r ted to dissociate the latter factor by habituating the rat to
periods of restraint of too short a duration to give rise to ulcers,
while respecting a sufficient interval between the periods of
immobilization.
Materials and Method
We used 30 Wistar rats, 10 males and 20 females, weighing 200
to 270 grams. These animals we divided into two groups of 15 rats,
evenly balanced in terms of sexes and weights. Restraint was always
carried out in metal tubes (2), in an air-conditioned room at a
temperature of 220C.
The rats of the first group were habituated to conditions of
restraint by 4 sessions of 6 hours each during which they were immo-
bilized in metal tubes. These 4 sessions were spread over a period
of 2 to 4 weeks, '. •especting an interval of 3 to 15 days (average,
6.6 days) bet`r,,.en periods of restraint. Three days after the fourth
session, the rats were subjected to a 24-hour period of restraint.
The rats of the second group were used as controls. They under-
went no habituation sessions and were subjected directly, at the same
time as the animals of the first group, to the 24-hour restraint
period.
1
<	 1
1
At the end of the 24-hour restraint period, the rats of both
groups were sacrificed, using ether The stomachs were examined,
Only ulcerous lesions were taken into account. These lesions are
considered severe wheel at least one of them has reached a diameter
of 3 mm.
Results
The table shows that the rats which were first habituated to
restraint are less susceptible to ulcers than the control animals;
this difference is significant (p<0.09). The difference is also
very clear when we compare the animals which were affected by serious
lesions. In this group in fact, we find only one rat habituated
to restraint, as opposed to 8 control rats. Habituation of the rat,
then, reduces both the occurrence and the severity of restraint
ulcers.
We also noted differences in the behavior of two groups of rats
with regard to restraint: the control rats spontaneously entered
the restraint tube, while the habituated rats showed an increasingly
market unwillingness, betraying the memory of previous stress. How-
ever, defecation by the rats, a barometer of their emotional condition,
gradually diminishes in the course of repeated restraint periods.
TABLE: COMPARISON OF THE OCCURRENCE OF ULCERS IN
RATS HABITUATED TO RESTRAINT AND IN CONTROL ANIMALS
Repeated restraint Control group
Saries NO. - of
rats
No.	 of rats
w/ulcers
No.	 o - rats
w/seri.ous
No. of—
rats
No of rats
w/ulcers
No .	 of
rats w/
ulcers serious
ulcers
1 5 f 3 1 5 f 4 4
2 5 m 0 0 5 m 3 1
3 5 f 1 0 5 f 3 3
Total 15 4 (27%) 1	 (7%) 15 10	 (67%) 8	 (53%)
!	 2
I '	 0
In each series the rats which were habituated to
restraint developed ulcers less frequently than the
control group.
Discussion
The cumulative ulcerogenous effect of repeated restraint can
predominate over habituation when the rat is subjected to long
periods of immobilization, separated by short intervals (3). Bonfils
(1), using 24-hour periods of restraint separated by free intervals
of 48 hours, notes a progressive reduction of recent ulcers (effect
of habituation) contrasting with an increase of Healing lesions
(cumulative effect). Guth and Mendick (4), subjecting rats to
daily but brief periods of restraint (4 hours) , observed as we did,
a gradual reduction in the occurrence of ulcers.
In our experiment we attempted to completely dissociate the
phenomenon oP habituation from the cumulative effects of respcting
an interval of three days between the last habituation session and
the final period of restraint and by using, for habituation, 6-hour
restraint periods. In our experimental conditions, a 6-hour restraint
period may be considered as subliminal because it gives rise to a
percentage of ulcer development of less than 10% (5).
The possibility of rats becoming habituated to restraint rules
out, in practice, the use for restraint test purposes of an animal
which has already been subjected to immobilization, even of short
duration.
Summary
The frequency and gravity of restraint ulcers are significantly
diminished in rats which 'lave previously been subjected to immobiliza-
tion of short duration. The habituation of the rat to conditions of
restraint probably explains this phenomenon.
3
M,
REFERENCES
1. S. Bonfils, G. Lieffoghe, X. Gelle, M. Dubra.squet and A.
Lambling, Rev. Franc. Et, Clin Biol., Vol, 5, p. 253, 1960,
2. M.S. Martin, F. Martin and R. Lambert, Digestion, Vol. 2, p.I	 p. 253, 1969,
3. D.A, Brodie and H.M. Hanson, Gastroenterology, Vol. 38, p. 353,
1960.
4. P.H. Guth and P. Mendick, Gastroenterology, Vol. 46, p. 285,
1964.
5. C. Andre, M.S. Martin, R. Lambert, and F. Martin, C.R. Soc.-
Biol., Vol. 163, p. 162, 1969.
ZN


Effect of habituation on the susceptibility of the rat to restraint ulcers

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