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Robert A Fox

Publications and source records attributed to Robert A Fox.

Self-Motion Perception and Motion Sickness

Motion sickness typically is considered a bothersome artifact of exposure to passive motion in vehicles of conveyance. This condition seldom has significant impact on the health of individuals because it is of brief duration, it usually can be prevented by simply avoiding the eliciting condition and, when the conditions that produce it are unavoidable, sickness dissipates with continued exposure. The studies conducted examined several aspects of motion sickness in animal models. A principle objective of these studies was to investigate the neuroanatomy that is important in motion sickness with the objectives of examining both the utility of putative models and defining neural mechanisms that are important in motion sickness.

Robert A Fox↗

Recovery of the vomiting reflex following area postrema ablation in squirrel monkeys

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) simulation 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. We feel that the relationship of postural control to motion sickness is an important one and one often overlooked. We reported the results of a study 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% of the same 11 animals became sick if they were unrestrained and maintained control of their posture.

Nancy G Daunton↗

Experimental studies of gastric dysfunction in motion sickness: The effect of gastric and vestibular stimulation on the vagal and splanchnic gastric efferents

The susceptibility of rhesus monkeys to motion sickens was investigated using test conditions that are provocative for eliciting motion sickness in squirrel monkeys. Ten male rhesus monkeys and ten male Bolivian squirrel monkeys were rotated in the vertical axis at 150°/s for a maximum duration of 45 min. Each animal was tested in two conditions, continuous rotation and intermittent rotation. None of the rhesus monkeys vomited during the motion tests but all of the squirrel monkeys did. Differences were observed between the species in the amount of activity that occurred during motion tests, with the squirrel monkeys being significantly more active than the rhesus monkeys. These results, while substantiating anecdotal reports of the resistance of rhesus monkeys to motion sickness, should be interpreted with caution because of the documented differences that exist between various species with regard to stimuli that are provocative for eliciting motion sickness.

Meryl L Corcoran↗

Conditioned taste aversion and motion sickness in cats and squirrel monkeys

The relationship between vomiting and conditioned taste aversion was studied in intact cats and squirrel monkeys and in cats and squirrel monkeys in which the area postrema was ablated by thermal cautery. In cats conditioned 7-12 months after ablation of the area postrema, three successive treatments with xylazine failed to produce either vomiting or conditioned taste aversion to a novel fluid. Intact cats, however, vomited and formed a conditioned aversion. In squirrel monkeys conditioned 6 months after ablation of the area postrema, three treatments with lithium chloride failed to produce conditioned taste aversion. Intact monkeys did condition with these treatments. Neither intact nor ablated monkeys vomited or evidenced other signs of illness when injected with lithium chloride. When the same ablated cats and monkeys were exposed to a form of motion that produced vomiting prior to surgery, conditioned taste aversion can be produced after ablation of the area postrema. The utility of conditioned taste aversion as a measure of subemetic motion sickness is discussed by examining agreement and disagreement between identifications of motion sickness by conditioned taste aversion and vomiting. It is suggested that a convincing demonstration of the utility of conditioned taste aversion as a measure of nausea requires the identification of physiological correlates of nausea, and caution should be exercised when attempting to interpret conditioned taste aversion as a measure of nausea.

area postrema↗

Investigating motion sickness using the conditioned taste aversion paradigm

The avoidance of foods which are associated with uncomfortable or aversive internal states has long been recognized. Many people are aware, either directly or via anecdotal reports, of individuals who avoid foods which were eaten just before the onset of sickness. Awareness of this phenomenon can be traced to the writings of John Locke. The disruption of diet during cancer therapy is sometimes ascribed to the attribution of an unpleasant quality to foods eaten preceding the sickness induced by therapy itself. In addition, it has long been recognized by the manufacturers of rodent poisons that animals avoid the injection of food treated with nonlethal doses of poison. An important part of the laboratory study of this phenomenon was directed toward studying the role learning plays in this type of avoidance behavior. Following the lead of Garcia and his associates, this avoidance has come to be interpreted as arising from a form of classical conditioning. In typical laboratory studies of this behavior, a novel food is ingested just prior to exposure to some stimulus, commonly poisoning or irradiation, which produces illness. Following the terminology of classical conditioning, it is common to describe this procedure as one of 'pairing' a conditioned stimulus (CS), the novel food, with an unconditioned stimulus (US), the illness induced by toxicosis or irradiation. Avoidance of the food in succeeding feeding opportunities is viewed as a learned response or a conditioned taste aversion (CTA). Garcia et al. asserted that motion sickness could produce 'gustatory' aversions, but passive motion was first reported as an US to establish CTA by Green and Rachlin. The purpose is to review the manner in which CTA has been used to study motion sickness. Numerous reviews concentrating on other aspects of CTA are available in the existing literature. Readers are encouraged to consult the various papers and edited books for extensive information on other aspects of this literature.

Robert A Fox↗

Conditioned taste aversion induced by motion is prevented by selective vagotomy in the rat

The role of the vagus nerve in motion-induced conditioned taste aversion (CTA) was studied in hooded rats. Animals with complete, selective gastric vagotomy failed to form conditioned taste aversion after multiple conditioning sessions in which the conditioned stimulus (a cider vinegar solution) was drunk immediately before a 30-min exposure to vertical axis rotation at 150 deg/s. Results are discussed with reference to the use of CTA as a measure of motion-induced 'sickness' or gastrointestinal disturbance, and because motion-induced CTA requires that both the vagus nerve and the vestibular apparatus be intact, in light of the possible convergence of vegal and vestibular functions.

Robert A Fox↗

Role of the area postrema in three putative measures of motion sickness in the rat

After thermal cauterization of the area postrema in rats, the absence of conditioned taste aversion of sucrose paired with lithium chloride (0.15M, 3.3 ml/kg) was used as a pharmacologic/behavioral index of area postrema damage. In a subsequent experiment the effects of area postrema lesions on three measures proposed as species-relevant measures of motion sickness were studied, using off-vertical rotation at 150 deg/s for either 30 or 90 min. Lesions of area postrema did not alter postrotational suppression of drinking or amount of defecation during motion. The initial acquisition of conditioned taste aversion to a novel cider vinegar solution paired with motion was not affected by lesioning of the area postrema, but these taste aversions extinguished more slowly in lesioned rats than in sham-operates or intact controls. Results are discussed in terms of proposed humoral factors which may induce motion sickness and in light of recent data on the role of the area postrema in similar measures in species possessing the complete emetic reflex.

Richard L Sutton↗

Effect of copper sulphate on the rate of afferent discharge in the gastric branch of the vagus nerve in the rat

The afferent nerve activity was recorded from a nerve filament isolated from the peripheral cut end of the gastric branch of the vagus nerve. The gastric perfusion of 4 ml of two different concentrations (0.04 percent and 0.08 percent) of CuSO 4 solution provoked an increase in afferent activity. The stimulating effect of the 0.08 percent solution was stronger than that of the 0.04 percent solution, and lasted for a longer period of time. The observations suggest a possible mechanism by which CuSO 4 elicits emesis.

Copper sulphate↗

Detection of emetic activity in the cat by monitoring venous pressure and audio signals

To investigate the use of audio signals as a simple, noninvasive measure of emetic activity, the relationship between the somatic events and sounds associated with retching and vomiting was studied. Thoracic venous pressure obtained from an implanted external jugular catheter was shown to provide a precise measure of the somatic events associated with retching and vomiting. Changes in thoracic venous pressure monitored through an indwelling external jugular catheter with audio signals, obtained from a microphone located above the animal in a test chamber, were compared. In addition, two independent observers visually monitored emetic episodes. Retching and vomiting were induced by injection of xylazine (0.66mg/kg s.c.), or by motion. A unique audio signal at a frequency of approximately 250 Hz is produced at the time of the negative thoracic venous pressure change associated with retching. Sounds with higher frequencies (around 2500 Hz) occur in conjunction with the positive pressure changes associated with vomiting. These specific signals could be discriminated reliably by individuals reviewing the audio recordings of the sessions. Retching and those emetic episodes associated with positive venous pressure changes were detected accurately by audio monitoring, with 90 percent of retches and 100 percent of emetic episodes correctly identified. Retching was detected more accurately (p is less than .05) by audio monitoring than by direct visual observation. However, with visual observation a few incidents in which stomach contents were expelled in the absence of positive pressure changes or detectable sounds were identified. These data suggest that in emetic situations, the expulsion of stomach contents may be accomplished by more than one neuromuscular system and that audio signals can be used to detect emetic episodes associated with thoracic venous pressure changes.

A Nagahara↗

Area postrema ablations in cats: Evidence for separate neural routes for motion- and xylazine-induced CTA and emesis

The effects of off-vertical rotation upon the Intake of tap water Immediately after rotation, and upon conditioned taste aversion, 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 predictions from similar experiments with human subjects where motion sickness develops more rapidly as the angle of tilt la Increased. It was suggested that off-vertical rotation may be a useful procedure for Insuring experimental control over vestibular stimulation In animal studies of motion sickness.

Robert A Fox↗

Current status: Animal models of nausea

The advantages, and possible benefits of a valid, reliable animal model for nausea are discussed, and difficulties inherent to the development of a model are considered. A principle problem for developing models arises because nausea is a subjective sensation that can be identified only in humans. Several putative measures of nausea in animals are considered, with more detailed consideration directed to variation in cardiac rate, levels of vasopressin, and conditioned taste aversion. Demonstration that putative measures are associated with reported nausea in humans is proposed as a requirement for validating measures to be used in animal models. The necessity for a 'real-time' measure of nausea is proposed as an important factor for future research; and the need for improved understanding of the neuroanatomy underlying the emetic syndrome is discussed.

Robert A Fox↗