8-OH-DPAT does not interfere with habituation to motion-induced emesis in cats.

Experiments were performed to determine if suppression of motion-induced emesis (motion sickness) by 8-OH-DPAT altered the development or retention of habituation to the motion stimulus. Cats received 8-OH-DPAT followed by provocative motion on three consecutive treatment days. A drug-free test on the fourth day resulted in an incidence of emesis that was not different from that obtained on the fourth consecutive day of drug-free motion testing. Three consecutive days of treatment with 8-OH-DPAT without motion had no effect on the incidence of motion sickness on the fourth day. It was concluded that suppression of motion sickness by 8-OH-DPAT does not alter the acquisition or retention of habituation.

Cerebrospinal fluid constituents of cat vary with susceptibility to motion sickness.

Six female cats, varying in susceptibility to motion sickness, were implanted with chronic cannulae in the rostral portion of the fourth ventricle. The cats were then challenged with a motion sickness-inducing stimulus. Samples of cerebrospinal fluid were withdrawn before and after emesis or 30 min of motion if emesis did not occur and again on control (no motion) days. The samples were analyzed by HPLC with an array of 16 coulometric detectors. Thirty-six compounds were identified in the samples. Baseline levels of DOPAC, MHPGSO4, uric acid, DA, 5-HIAA and HVA were lower on motion and control days in cats which became motion sick when compared with cats which did not become motion sick. None of the identified compounds varied as a function of either exposure to motion or provocation of emesis. It is concluded that susceptibility to motion sickness is a manifestation of individual differences related to fundamental neurochemical composition.

8-OH-DPAT suppresses vomiting in the cat elicited by motion, cisplatin or xylazine.

Vomiting was suppressed in cats pretreated with 8-OH-DPAT and then challenged with an emetic stimulus; motion, xylazine or cisplatin. The antiemetic effect is likely due to stimulation of postsynaptic serotonin-1A receptors. The most parsimonious explanation is that it acts at a convergent structure, presumably at or near the vomiting center. If so, 8-OH-DPAT may block emesis elicited by virtually any other stimulus. A supplementary experiment revealed that lorazepam suppressed motion sickness at a dose that produced ataxia, but did not suppress xylazine-induced emesis. These results do not support the possibility that the antiemetic effects of 8-OH-DPAT were the result of anxiolytic activity.

Systemic naloxone increases the incidence of motion sickness in the cat.

Subcutaneous injections of naloxone in a total dose of 0.4 mg or greater one hour before a swing stimulus increased the frequency of motion sickness symptoms and shortened the latency of retching and vomiting.

A stimulator for laboratory studies of motion sickness in cats.

A motion sickness device is described which produces motion sickness in about 40% of an unselected population of unrestrained female cats during a 30-min exposure at 0.28 Hz. The apparatus provides a gentle wave stimulus, similar to that provided by an amusement park Ferris Wheel. Two cats may be tested at the same time. This device is useful for studies of putative antimotion sickness drugs or the biochemical basis of the emetic response to motion.

Buspirone blocks motion sickness and xylazine-induced emesis in the cat.

Cats were tested for motion sickness following s.c. pretreatment with four doses of buspirone. Buspirone blocked motion sickness with an ED50 of 0.46 mg . kg-1 base. Buspirone pretreatment (4.0 mg . kg-1 base) also significantly blocked vomiting in cats later injected with 0.66 mg . kg-1 (base) s.c. of the emetic drug xylazine. The results are interpreted as showing that buspirone is acting at the vomiting center, the point of convergence for the separate mechanisms subserving chemically-induced emesis and motion sickness.

Habituation of motion sickness in the cat.

We subjected 30 female cats to a motion sickness stimulus in three series of tests. A series consisted of five tests given bi-weekly, weekly, or daily. Each test consisted of 30 min of stimulation followed by 1 min of rest, and series were separated by a period of not less than 14 d. Retching was the dependent variable. No habituation (reduction in the incidence of retching) was found with biweekly testing but pronounced habituation was observed with weekly and daily testing. The 30 cats were divided evenly into high and low susceptibility groups based on the results of the biweekly tests. The rate of habituation was the same for the two susceptibility groups in both the weekly and daily series.

Motion sickness in cats: a symptom rating scale used in laboratory and flight tests.

The cat is proposed as a model for the study of motion and space sickness. Development of a scale for rating the motion sickness severity in the cat is described. The scale is used to evaluate an antimotion sickness drug, d-amphetamine plus scopolamine, and to determine whether it is possible to predict sickness susceptibility during parabolic flight, including zero-G maneuvers, from scores obtained during ground based trials.

Vasopressin and motion sickness in cats.

Levels of arginine vasopressin (AVP) in blood plasma and cerebrospinal fluid (CSF) were measured in cats under several motion-sickness-inducing conditions. Plasma AVP increased significantly in both susceptible and resistant animals exposed to motion. When vomiting occurred, levels of plasma AVP were dramatically elevated (up to 27 times resting levels). There was no difference in resting levels of AVP of susceptible and resistant cats. Levels of CSF-AVP were not elevated immediately after vomiting, but the resting levels of CSF-AVP were lower in animals that vomited during motion than in those animals which did not vomit during motion. The results of these experiments show that changes in systemic AVP are directly related to vomiting induced by motion, however, CSF-AVP apparently does not change in association with vomiting. CSF-AVP does appear to be lower in animals that reach frank vomiting during motion stimulation than in animals which do not vomit.

Research strategies for motion and space sickness.

Research is urged for several motion sickness topics now receiving relatively little attention. The role of the area postrema, if any, is not completely resolved. The hypothesis that the cerebral spinal fluid might be a necessary neurochemical conduit should be confirmed or put to rest. It is surprising that the cerebellum, implicated more than 40 years ago, has not been reevaluated for its role in motion sickness in view of the explosion of new data on this structure. The sensory rearrangement theory, known by several names, needs direct experimental verification. One such experiment should determine if vestibular input is an essential element. Data interpretation problems related to rates of adaptation, often a consideration in sensory rearrangement experiments, are explored. The most exciting gains are to be achieved through neuropharmacologic approaches, particularly by exploiting the unique advantages offered by animal models.

Statistical analysis of censored motion sickness latency data using the two-parameter Weibull distribution.

The suitability of the two-parameter Weibull distribution for describing highly censored cat motion sickness latency data was evaluated by estimating the parameters with the maximum likelihood method and testing for goodness of fit with the Kolmogorov-Smirnov statistic. A procedure for determining confidence levels and testing for significance of the difference between Weibull parameters is described. Computer programs for these procedures may be obtained from an archival source.

Xylazine emesis, yohimbine and motion sickness susceptibility in the cat.

The possible role of the alpha-2 adrenoceptors in xylazine-induced vomiting and in motion sickness was investigated. Cats were divided into two groups according to motion sickness susceptibility and were observed after s.c. injections of xylazine. The incidence of vomiting increased with the dose, and at each dose, the high susceptibility group had a greater emetic incidence than the low susceptibility group. In another experiment with cats divided into two groups according to motion sickness susceptibility, s.c. administration of yohimbine effectively antagonized the xylazine-induced emesis in both susceptibility groups. The cats in the latter experiment were then challenged with a motion sickness stimulus, after s.c. pretreatment with yohimbine. Yohimbine failed to prevent motion sickness but did occasion an unexplained variability in the incidence of vomiting. These findings suggest that the emetic effect of xylazine results from stimulation of alpha-2 adrenoceptors but that these receptors are not fundamental to feline motion sickness. The fact that susceptibilities to xylazine-induced emesis and to motion sickness are correlated suggests a point of interaction other than the area postrema, which is known to be essential for xylazine-induced vomiting but not for motion sickness in the cat.

Evidence for a motion sickness agent in cerebrospinal fluid.

The possibility that there might be a neurohumoral cerebrospinal fluid (CSF) link in motion sickness was directly tested in cats by blocking the flow of CSF from the third into the fourth ventricle. Evidence obtained thus far is consistent with the hypothesis. Cats with demonstrably sound blocks did not vomit in response to an accelerative motion sickness stimulus, whereas cats with imperfect 'leaky' blocks vomited with little or no increase in latency. Although there are several putative candidates, the identification of a humoral motion sickness substance is a matter of conjecture.