Current theory and recent evidence suggest that motion sickness occurs under conditions of sensory input in which the normal motor programs for producing eye, head, and body movements are not functionally effective, i.e. under conditions in which there are difficulties in maintaining posture and controlling eye movements. Conditions involving conflicting or inconsistent visual-vestibular (VV) stimulation should thus result in greater sickness rates since the existing motor programs do not produce effective control of eye-head-body movements under such conditions. It is felt that the relationship of postural control to motion sickness is an important one and one often overlooked. The results are reported which showed that when postural requirements were minimized by fully restraining squirrel monkeys during hypogravity parabolic flight, no animals became motion sick, but over 80 percent of the same 11 animals became sick if they were unrestrained and maintained control of their posture

Daunton, Nancy G.

Fox, Robert A.

English

NASA Technical Reports Server

The Physiologist, Vol. 28, No. 4
Q
N94-2 905
49.19
AREA POSTREMA ABLATIONS IN CATS: EVIDENCE FOR SEPARATE NEURAL
ROL_ES FOR MOTION- AND XYLAZINE-INDUCED CTA AND EMESIS.
M. Corcorani! R. Fox _, K. grtzzee*, G. Crampton i, and
N. Daunton* (SPON: J. Zabara). NASA Ames Research Center,
Hoffett Field, CA. 94035; San Jose State Univ., San Jose, CA.
95192; Delta Regional Primate Center, Covington, Lb. 70433;
Wright State Univ., Dayton, OH. 45435.
Previous studies on the role of the area postrema (A_) in
vomtttn_ induced in the cat by motion and drugs have shc_a_that
the AP Is not essential for motion-Induced vomiting, but Is
necessary for vomiting to apomorphtne and xylaztne. To confirm
these findings and to determine the role of the AP in the for-
mation of Conditioned Taste Aversion (CTA), the AP was ablated
bilaterally in lO adult female cats. With one exception, the
ablated cats continued to vomit to the sam_ motion that elicit-
ed emests before the ablation. Doses of xTlaztne and apomorph-
fne that elicit emesfs in intact cats, failed to induce emeats
in the ablated cats. Histological examination indicated that 8
cats had complete lesions and 2 had partial lessons. Invest-
igations of effects of AP ablations on CTA revealed that cats
with complete lesions did not form CTA to flavored mllk paired
with rylazine InJecclons. However, cats wlth partlal lesions
developed xTlazlne-lnduced CTA. Seven of the 8 completely les-
toned cats developed motion-Induced CTA, even though emests
was not conslstentl7 elicited by motion. These results suggest
that there are multiple routes for inducing CTA and the emetic
reflex, that CTA can form wlthout eltcttlng emesta, and that
CTA may be a sensitive measure of sub-emetic motion sickness.
330
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Off-Vertical Rotation Produces Conditioned
Taste Aversion and Suppressed Drinking
in Mice
ROBERT A. FOX, B.A., PH.D., ANDREA H. LAUBER, B.A.,
M.A., NANCY G. DAUNTON, M.A., PH.D., MARILYN
PHILLIPS, B.A., and LINDA DIAZ, B.A., M.A.
San Jose State University, San Jose, California 95192 and
NASA-Ames Research Center, Moffett Field, CA 95035
Fox RA, LAUBER AH, DAUNTON NG, PHILLIPS M, and DIAZ L. Off-
Vertical rotation produces conditioned taste aversion and suppressed
drinking in mice. Aviat. Space Environ. Med. 1984;55:632-5.
The effects of off.vertical rotation upon the intake of tap water
immediately after rotation, and upon conditioned taste aver-
sion, were assessed in mice with the tilt of the rotation axis
varying from 5 to 20* from the earth-vertical. Conditioned taste
aversion occurred in all mice that were rotated, but the intake
of tap water was suppressed only in mice that were rotated at
15 or 20* of tilt. The greater suppression of tap water intake
and the stronger conditioned aversion in the mouse as the angle
of tilt was Increased in this experiment are consistent with pre-
dictions from similar experiments with human subjects where
motion sickness develops more rapidly as the angle of flit is
Increased. It was suggested that off-vertical rotation may be a
useful procedure for insuring experimental control over vestib-
ular stimulation in animal studies of motion sickness.
OST STUDIES OF MOTION sickness involving
animal subjects use procedures in which the an-
imals are permitted some voluntary movement during
exposure to the sickness-inducing motion. In fact, vol-
untary motion is necessary to obtain motion sickness
axis rotation (12), moving a rotating disk through an arc
on the arm of a seesaw (2), alternating 15-s periods of
rotation with 5-s periods of no rotation (6,11), and using
sinusoidal yaw axis rotation (7). All of these methods
involve complex vestibular stimuli which are often dif-
ficult to quantify and to generate. A simple method for
producing specified vestibular stimulation which makes
animals motion sick in the absence of voluntary move-
ment could be useful for future studies.
It is known that motion sickness can be induced
readily in human subjects producing no voluntary
movement if rotation about an axis displaced from
earth-vertical is used as the eliciting stimulus (3,8). The
effects of various degrees of off-vertical rotation have
not been evaluated previously in animal studies. The
experiment reported here was conducted as a pelimi-
nary examination of the usefulness of this stimulation
as a method of generating controlled vestibular stimu-
lation in animals. Mice were used as subjects in this
study and conditioned taste aversion and drinking
in human and animals subjects during vertical axis ro- suppression were used as measures of the effects of
tation if the subjects are located on or close to the axis vestibular stimulation.
of rotation (10). Methods for insuring that vestibular
stimulation will result from rotation even if voluntary
movement does not occur or is reduced have involved
combining sinusoidal vertical accelerations with vertical
Authors R. A. Fox, A. H. Lauber, M. Phillips, and L. Diaz are
with San Jose State University, and N. G. Daunton is with NASA-
Ames Research Center.
This manuscript was received for review in August 1983. The re-
vised manuscript was accepted for publication in March 1984.
METHODS
Subjects: The mice, 72 male Swiss-Webster weighing
20-23 g, were housed 6 per cage and maintained on a
12:12 light:dark cycle. Animals were assigned randomly
to one of six treatment groups with 12 mice in each
group.
Apparatus: The off-vertical rotation device consisted
of an aluminum disk mounteddirectly on the shaft of a
gear reduction box driven by a Bodine motor. This disk
632 Aviation, Space, and Em,ironmental Medicine • July, 1984
OFF-VERTICAL ROTATION_FOX ET AL.
rotated clockwise at 204°-s -] (34 rpm). Holding cages
were constructed by placing two plexiglass dividers into
aluminum chassis boxes (6.5 cm wide x 24.0 cm long
× 12.8 cm high) to form three compartments (6.5 cm
×8.0 cm × 12.8 cm) in each chassis .box. Four such
_ _[_oxes were mounted perpendicular to the four radii of
the disk, 12 cm from the axis of rotation. Thus, each
mouse was positioned 12.0 to 15.0 cm from the axis of
rotation. With the angular velocity of 204°-s - J, forces
of 0.16 and 0.19 G occurred at 12.0 and 15.0 cm dis-
tances from the axis of rotation. Tilt was accomplished
by elevating one end of the device to produce tilts of
the axis of rotation of 0, 5, 10, 15 and 20° from the earth
vertical. The vertical excursion resulting from off-ver-
tical rotation produced an additional force of up to
+ 0.05 G at the tilt angle of 20° with lesser forces at the
smaller angles of tilt.
Procedure." During the first 6 d of the experiment the
mice were adapted to a restricted drinking regimen.
Each d the mice were placed into individual cages and
allowed to drink from a 20-ml pipette inserted into each
cage. The animals had access to tap water for 10 min.
Water was then removed for 15 min (a rest period).
After this period the animals were given access to tap
water and food in the individual cageg for an additional
20 min. Thus, the mice had access to water for 30 min
(I0 min plus 20 min) each d. The intake of fluid during
the two drinking periods was determined from pipette
readings.
On Day 7 mice were offered a sweet flavored solution
(2 g saccharin.L-i of tap water) during the initial 10-
rain drinking period. This drinking period was followed
immediately by exposure to rotation for 15 min at one
of the five angles of tilt, or, for the control group, by
confinement in a stationary apparatus for 15 rain. The
next 2 d were for recovery and the same drinking reg-
imen used during the adaptation period (tap water in
each drinking period) was repeated. On Day 10 the mice
were again offered the flavored solution during the first
10-rain drinking period, which was followed by the 15-
min rest period, and finally by the 20-min period in
which access to both food and tap water was given.
RESULTS
The effects of angle of tilt were assessed using
suppression of drinking following rotation and condi-
tioned taste aversion as measures. General suppression
of drinking produced by rotation was determined by
measuring the intake of tap water immediately after ro-
tation. The average intake of fluid by each group is
shown in Fig. 1. There was no difference between con-
trois and rotated animals in the intake of tap water
during the 20-min drinking period on the day preceding
the rotation [F(5,66)<1]. However, immediately after
rotation, the intake of tap water decreased as the angle
of tilt increased [F(5,66)=2.70; p<0.05]. The relation-
ship between intake of tap water and angle of tilt was
examined further using Dunnett's Test to compare re-
sults from all treatment groups with those from the con-
trol group. This test indicated that after rotation, intake
of tap water was suppressed for tilt angles of 15 and 20°
(ps<0.05) but that the response of the groups exposed
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SACCHARIN
I I I 1 I I
Control 0 5 10 15 20
AXIS TILT ANGLE (dog)
Fig. 1. Average consumption of saccharin water (3 d after con-
ditioning) and of tap water (immediately after rotation) by the
control subjects and by the animals rotated at various angles of
tilt from earth-vortical.
to other angles of tilt did not differ from that of the
control group (ps>0.05).
The conditioned taste aversion produced by varying
angles of tilt was assessed by determining differences
in the consumption of saccharin flavored water 3 d after
the rotation. Prior to rotation the control and rotation
groups did not differ in the amount of saccharin water
drunk [F(5,66)= 1.33, p>0.25]. Following the rotation,
however, conditioned taste aversion was present in all
treatment groups [F(5,66)= 5.06, p<0.005]. Compar-
ison of results from all treatment groups with those from.
the control group using Dunnett's test, reflected a lower
intake of saccharin water by animals that were rotated
than by the non-rotated control animals (p<0.05 for tilt
angles of 0 and 5" and ps<0.01 for tilt angles of 10, 15
and 20°).
The linear correlation of the average intake of fluid
of each treatment group with the angles of tilt of 0-20 °
was determined for both tap water (suppression of
drinking measures, r=-0.89) and saccharin flavored
water (taste aversion measure, r = - 0.63). This analysis
indicates that the tap water variable used to assess the
suppression of drinking reflects a stronger linear rela-
tionship with the angle of tilt than does the conditioned
taste aversion measure (i.e., saccha ,'z- ;ntake). In ad-
dition, the regression line for ,ap water predicts intake
Aviation, Space, and Environmental Medicine • July, 1984 633
'OFF-VERTICAL ROTATION--FOX ET AL.
3. Graybiel, A., and E. E Miller II. Off-vertical rotation: A conve-
nient precise means of exposing the passive human subject to
a rotating linear acceleration vector. Aerospace Med. 41:407-
410; 1970.
4. Graybiel, A., C. D. Wood, E. E Miller, and D. B. Cramer. Diag-
nostic criteria for grading the severity of acute motion sickness.
Aerospace Med. 39:453-455; 1968_.
5. Green, L., and H. Rachlin. Learned taste aversions in rats as a
function of delay, speed, and duration of rotation. Learn.
Motiv. 7:283-289; 1976.
6. Haroutunian, V., D. C. Riccio, and D. E Gans. Suppression of
drinking following rotational stimulation as an index of motion
sickness in the rat. Physiol. Psychol. 4:467-472; 1976.
7. Igarashi, M., H. Isago, T. O-Uchi, W. B. Ku|ecs, J. L. Homick,
and M. E Reschke. Vestibular-visual conflict sickness in the
squirrel monkey. Acta Otolarygol. 95:!93-198; 1983.
g. Miller, E. E II, and A. Graybiel. A provocative test for grading
susceptibility to motion sickness yielding a single numerical
score. Acta OtolaD'ngol. [Suppl.]:274-296; 1970.
9. Mitchell, D., M. L. Krusemark, and E. Hafner. Pica: A species
releva_nt )2ehavioral assay of motion sickness in the rat. Phy-
siol. Behav. 18:i25-130; 1977.
10. Money, K. E. Motion sickness. Physiol. Rev. 50:1-39; 1970.
!1. Ossenkoop, K.-P., and N. L. Frisken. Defecation as an index of
motion sickness in the rat. Physiol. Psychol. 10:355-360; 1982.
12. Roy, M. A., and K. R. Brizzee. Motion sickness-induced food
aversions in the squirrel monkey. Physiol. Behav. 23:39-41;
1979.
Aviation, Space, and Environmental Medicine • July, 1984 635
OFF-VERTICALROTATION--FOXETAL.
by thecontrolanimals, which were not rotated, while
the regression line for the saccharin variable does not
predict intake by the saccharin control animals.
DISCUSSION
The results of this study show that off-vertical rota-
tion produces effects on conditioned taste aversion and
drinking suppression--two putative measures of mo-
tion sickness (1,5,6,9)--which would be predicted from
human studies of motion sickness using off-vertical ro-
tation. Miller and Graybiel (8) have reported a close
linear relationship between the logarithmically scaled
off-vertical angle of tilt and the time to evoke malaise
IIA in man with tilt angles of 7.5-25 ° (see [4] for a
description of the sickness rating scale). To compare the
results of this study with those of Miller and Graybiel,
the correlations of angles of tilt with each of the mea-
sures of "sickness" was determined for the range from
0-20 ° of tilt (see Fig. l). As the angle of tilt increases,
both measures reflect the increasing effects of rotation
in mice as in man.
When all of the groups that were rotated at the var-
ious angles of tilt were compared with the non-rotated
control group, the effects of tilting were found to be
different for the two measures. As reflected by the con-
ditioned taste aversion measure, intake of the saccharin
solution was suppressed in all groups that were rotated.
On the other hand, if suppression of tap water intake
immediately after rotation was used as the measure,
significant effects were found only for the two groups
rotated at the two greatest angles of tilt (15 and 20°),
i.e., where the vestibular stimulation was greatest.
These results indicate that conditioned taste aversion is
a more sensitive measure of the aversion effects of ves-
tibular stimulation than is suppression of the intake of
a familiar fluid immediately after rotation. This result
also implies that the taste aversion paradigm might be
preferred if treatment effects are expected to be small.
It should be kept in mind, however, that the sensitivity
of this measure might result in "floor effects" if motion
parameters are severe. On the other hand, the mea-
surement of water intake is obtained more easily than
the measurement of taste aversion and might be consid-
ered the preferred measure of the effects of motion be-
cause of the continuous relationship observed between
intake of water and angle of tilt in this experiment.
In discussing the measure involving post-rotary in-
take of tap water, is should be noted that with the
drinking regimen used in this experiment the suppres-
sion of this intake might be affected by transient effects
of the motion (e.g., ataxia from vestibular stimulation)
rather than by motion-induced "sickness" per se. Two
observations indicate that transient disruptive effects
are not the sole cause of the suppression of drinking.
First, the animals were able to drink immediately fol-
lowing rotation as evidenced by the fact that they often
drank a small amount of water immediately on being
placed into the drinking area. Second, no quantifiable
ataxia or other motor disruption was observed during
the drinking sessions. In addition, it was possible to
compare the intake of water during each half of the 20-
min drinking period which followed the motion treat-
ment. If drinking were suppressed by disruption of
motor responses, intake might be expected to increase
with recovery after rotation. In fact, the opposite oc-
curred on treatment days with motion and as well as on
control days with no motion. While these observations
might suggest that intake of water after rotation reflects
"sickness" rather than inability to drink due to disrup-
tion of motor control, such an interpretation is not re-
quired, and it must remain a subset of the larger ques-
tion of how to interpret "motion sickness" in species
which do not have a complete emetic reflex.
This same argument regarding transient disruption of
motor systems does not apply to conditioned taste av-
ersion because the magnitude of this aversion was as-
sessed in a test made 3 d after the motion treatment. In
spite of this 3-d recovery period, conditioned aversion
appears to be a more sensitive measure of the effects
of off-vertical rotation than the measure involving in-
take of tap water immediately after rotation. Further
evidence for the sensitivity of conditioned taste aver-
sion can be found in the demonstration that squirrel
monkeys form conditioned aversions under motion
sickness-evoking conditions even when emesis does not
occur (12). It is not known whether the neural mecha-
nisms involved in the formation of conditioned aver-
sions are the same as those which lead to emesis, but
the fact that conditioned taste aversions do develop
without emesis suggets that such aversions could pro-
vide a sensitive measure of pre-emetic symptoms of mo-
tion sickness (e.g., nausea).
The effects of angle of tilt as reflected by conditioned
aversion and drinking suppression in the mouse show
that the mouse is affected by this stimulation in a
manner that is predictable from studies of motion sick-
ness in humans. This finding provides support for the
use of off-vertical rotation in studies of motion sickness
in animals since the stimulus to the vestibular apparatus
can be specified quite precisely and varied easily when
the voluntary movement of the animals is inhibited. Al-
though there may be some question as to whether off-
vertical stimulation is specific to the otolithic receptors
or whether it also produces some canal stimulation (3),
it is clear that off-vertical rotation of restrained animals
would result in a much more controlled stimulation of
the vestibular apparatus than is found in the typical an-
imal study of motion sickness in which voluntary move-
ments are neither controlled nor measured and volun-
tary movements by the animals might result in unspec-
ified and undesirable cross-coupled accelerations.
ACKNOWLEDGMENTS
Funds for this study were provided under Interchange Agreement
NCA 2-OR-675-801 by Ames Research Center, NASA, Moffett Field,
CA, and by NIH Grant S06RR08192-02 to Robert A. Fox.
All procedures used in this project complied with the Guideline
Principles in the Care and Use of Animals.
REFERENCES
1. Braun, J. J., and H. Mclntosh, Jr. Learned taste aversions in-
duced by rotational stimulation. Physiol. Psychol. 1:301-304;
!973.
2. Fox, R. A., and N. G. Daunton. Conditioned feeding suppression
in rats produced by cross-coupled and simple motions. Aviat.
Space Environ. Med. 53:218-220; 1982.
634 Aviation, Space, and Environmental Medicine • July, 1984


Motion sickness elicited by passive rotation in squirrel monkeys

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