Subjective concomitants of motion sickness: quantifying rotation-induced illness in squirrel monkeys.

It has been suggested by numerous researchers that the development of conditioned food aversion (CFA) in experimental animals represents the presence of a subjective state of illness. Squirrel monkeys with proven susceptibility to rotation-induced vomiting were given surgical bilateral labyrinthectomies, a procedure known to abolish signs and symptoms of motion sickness in human beings. Postoperatively, labyrinthectomized monkeys neither vomited nor revealed any reduction in food consumption when exposed to provocative rotation. Other samples of monkeys known to be refractory to horizontal rotation and to sinusoidal vertical motion also exhibited little tendency to acquire a conditioned aversion to banana. But monkeys who had sham operations and those who revealed weak-to-strong signs of motion sickness exhibited a marked CFA (significant reduction in food intake). The strength of CFA was much greater when elicited in the test vehicle when compared with response in the home cage. The findings are interpreted as support for a limited application of CFA procedures for inferring the presence of motion-induced nausea and malaise.

Adaptation and habituation of motion-induced vomiting in squirrel monkeys.

Nonrestrained adult squirrel monkeys were found to be prolific vomiters when rotated in the horizontal plane for at least 1 h with visual cues available. When multiple daily spins were given, monkeys who vomited early during the first session tended to habituate during subsequent rotations. Subjects who vomited late during the first spin tended to vomit increasingly earlier for several days before the trend reverted to habituation. When a single rotation was continued for up to 8 h, emetic waves occurred with a high probability density for about 2 h, then ceased for many hours with an occasional animal exhibiting isolated emetic episodes. Adaptation effects were transient; when retested beyond a week, most subjects vomited in less time than did inexperienced monkeys on their first exposure to rotation. Attempts to confirm the findings using sinusoidal vertical acceleration were unsuccessful because of failure to induce vomiting using this type of motion.

A two-factor model of rotation-induced motion sickness syndrome in squirrel monkeys.

Nonrestrained squirrel monkeys were rotated repeatedly in the horizontal plane once per day for preset times or until a vomiting response occurred. Emesis latencies and frequencies were recorded. Some subjects were fed fresh banana immediately before and after each rotation. The amount consumed provided a measure of conditioned food aversion or feeding suppression. A two-factor model of the motion-sickness syndrome was formulated to account for the data. According to the model, appropriate stimulation of the semicircular canals accompanied by visual and proprioceptive stimulation generates two independent physiologic processes or states: an objective emesis and a subjective nausea process. The emesis process is revealed by vomiting responses and the nausea process is inferred from the appearance of conditioned food aversion. Susceptible monkeys (type I) and resistant monkeys (type II) have different emesis processes, but both have similar nausea processes. Refractory monkeys have no well-developed emesis or nausea processes. Time and order characteristics of the motion-sickness syndrome depend on specific interactions of emesis and nausea processes.

Motion-induced sickness following bilateral ablation of area postrema in squirrel monkeys.

Using squirrel monkeys as experimental subjects, we reexamined the disputed role of the area postrema (AP) in motion-induced vomiting. After anesthetization, the obex and rhomboid fossa were exposed surgically, and the AP was ablated by thermal coagulation using either a battery cautery or a CO2 microsurgical laser. Sham operations were performed on another sample of monkeys. Two or more weeks after surgery, all animals were given 10 daily 2-hour horizontal rotations at 30 rpm. Every monkey in both the lesions and sham samples vomited on two or more test days. While the vomiting characteristics were modified following ablation of AP, its function is not indispensible for the development of motion sickness in horizontally-rotated squirrel monkeys.

Intensification and habituation of experimental motion sickness in squirrel monkeys by repeated horizontal rotation.

The aim of this research was to quantify the development of habituation or intensification of experimental motion sickness induced in Bolivian squirrel monkeys by repeated exposures to horizontal rotation. Incidence, frequency, and latency of vomiting responses were recorded from monkeys rotated daily in a transparent testing chamber at 30 rpm for periods of 1 or 2 hours. Data showed that more than half of the subjects revealed habituation in terms of increased latencies for vomiting. Some showed a tendency to vomit increasingly earlier with multiple daily exposures to rotation. The development of habituation and intensification was evident as early as the second day of rotation. The number of emetic episodes per day decreased as a consequence of repeated rotation, but intensification of vomiting frequency did not occur beyond the fifth day.

Effects of head and body restraint on experimental motion-induced sickness in squirrel monkeys.

Each of 16 Bolivian-phenotype squirrel monkeys of mixed sex had a machine bolt mounted on the skull with acrylic cement; 13 were provided with temporary plaster body casts allowing free movement. With eyes open, all were rotated in the horizontal plane at 30 rpm every other day until vomiting occurred or for a maximum duration of 120 min/spin. Latencies for motion-sickness signs were recorded under three experimental conditions: free movement, torso fixed to an aluminum frame and both torso and head restrained by bolting to the frame. Subsequently, 10 monkeys from this sample were rotated while blindfolded with head and torso immobilized. Results partially confirmed human and animal findings reported by others: reduced mobility was accompanied by a reduction in the incidence and an increase in the latency of motion sickness. The importance of optokinetic input for the generation of motion sickness in this species was clear.

Behavioral conditioning and experimental motion-induced sickness.

Adult male squirrel monkeys were the subjects of experiments conducted to determine whether or not repeated exposures to sickness-inducing horizontal rotation would result in behavioral conditioning of emetic responses. The development of conditioned food aversion and feeding suppression as a consequence of pre- and postrotation eating was quantified. It was concluded that neither instrumental conditioning nor classical conditioning were valid alternative hypotheses for the occurrence of repeated vomiting episodes over a period of ten daily exposures to motion. Conditioned aversion to fresh banana and feeding suppression developed gradually if rotation, which induced multiple bouts of vomiting, was sustained for 1- or 2-hour sessions. If spinning was terminated immediately after the first emetic response, no aversion or suppression emerged. The occurrence of food aversion, by itself, is questioned as a valid index of the presence of subjective concomitants of motion sickness in animals.

Neurohumoral hypothesis of motion-induced vomiting. Communication.

The current status and implications of the neurohumoral hypothesis of motion-induced vomiting are reviewed. Data show that squirrel monkey subjects vomit only once if horizontal rotation is terminated immediately on the occurrence of the emetic response. Refractory periods for multiple vomiting episodes concurrent with continued rotation are sufficiently brief to suggest that the expected presence of the hypothetical neurochemical agent in the cerebrospinal fluid of the fourth ventricle should continue to evoke more than one vomiting response even after cessation of motion stimulation. In its present form, the hypothesis is conceptually vague and should be developed further to account for a mechanism by which the expected recurrent emesis is inhibited during the period when the alleged agent is a potentially effective stimulant.

Experimental motion sickness induced in squirrel monkeys by continuous off-axis horizontal rotation.

Under a variety of experimental conditions, nonrestrained adult male squirrel monkeys were subjected to continuous rotation in the horizontal plane at 33 rpm. Severity of motion-induced sickness was quantified by measuring latencies of three responses associated with sickness. Per- and postrotational nystagmus was recorded from a subsample of monkeys with permanent recording electrodes implanted in the bony orbits. Incidence of sickness depended on the time limits of stimulation imposed, and it occurred in a maximum of about 90 per cent of test sessions if rotation was continued for two hours. When subjected to ten once-per-day rotation sessions, only a few monkeys showed evidence of developing transient habituation of onset of motion sickness. Mean frequency of emetic episodes, however, declined over the latter half of the rotation series. Restricting visual cues by blindfolding the monkeys prevented most subjects from vomiting.

Horizontal nystagmus in methylmercury poisoned squirrel monkeys.

Chronic states of methylmercurialism were induced in squirrel monkey subjects. Principal neurological signs included ataxia, abnormal gait, incoordination and amaurosis. Although slight to moderate vacuolization occurred in supporting cell layers of the cristae and maculae, receptor cell function was essentially normal. Except for a lowered cold threshold, bithermal caloric-induced nystagmus was not significantly different from control values. Pre and postrotatory (Barany chair) tests revealed a reduction only in frequency related variables. The development of spontaneous and positional nystagmus (sometimes with eyes open) coupled with the behavioral signs and the evidence of normal receptor response suggested cerebellar dysfunction. Severe pathologic changes were present in the cerebral cortex, but no lesions were found in the cerebellar cortex. Substantial neuronal degeneration and gliosis, however, were observed in several subcortical nuclei, including cerebellar and vestibular nuclei.

Effectiveness of the CO2 laser in experimental tympanic neurectomy.

As one of a series of investigations to evaluate the efficacy and safety of CO2 lasers in otologic microsurgery, squirrel monkeys were subjected to tympanic neurectomies by means of vaporizing Jacobson's nerve in the promontory region. Air and bone conduction hearing acuity was measured by computer-averaged pure tone evoked responses and behavioral audiometry before and after laser surgery. A moderate (avoidable) conductive loss was found as a consequence of the surgical approach selected, but no significant sensorineural loss was apparent. Thus, there would appear to be no adverse cochlear side effects as a result of using this instrument in the middle ear. The laser neurectomy procedure, however, was no more effective for the clinical purposes for which it was proposed than those techniques reported by several other investigators.

Experimental lead paint poisoning in nonhuman primates. III. Pathologic findings.

Necropsies were performed on 25 rhesus monkeys, three cebus monkeys and three baboons which had been fed leaded paint or lead acetate at various doses up to 666 days. The 31 test primates and six controls ranged in age from five days to about eight years. In addition, the brains of 13 subadult squirrel monkeys fed lead oxide and two controls were studied grossly and microscopically. Lead content of liver, kidney and brain correlated with clinical outcome and typical histologic changes. Neuropathologic lesions, most severe in the young, occurred in 28 of 43 test primates despite a paucity of neurological signs. Brain lesions were similar to those occurring in human lead encephalopathy and included degenerative and proliferative changes of small vessels, ring hemorrhages, edema, perivascular hyalin droplets, rosette-like deposits of proteinaceous exudates, focal loss of myelin, astrogliosis and necrosis of hippocampal neurons.