http://www.users.miamioh.edu/smartlj/S%26S_BRB98.pdf

Postural instability precedes motion sickness.

Mitchell et al. (1976, 1977) suggested that pica, eating of nonnutritive substances such as kaolin, is an illness-response behavior in rats. In the present study, we first confirmed their suggestion and then examined the effects of antiemetics on emetic-induced pica in rats. Intraperitoneal injection of apomorphine induced dose-dependent kaolin consumption. Pretreatment with domperidone inhibited apomorphine-induced kaolin intake. Oral administration of copper sulfate and intraperitoneal injection of cisplatin also induced dose-dependent kaolin consumption. Pretreatment with ondansetron inhibited cisplatin-induced kaolin intake. These findings suggest that pica in rats was induced through 1) dopamine D2 receptors in the chemoreceptor trigger zone, and 2) the stomach, partly via 5-HT3 receptors in the visceral afferents in the stomach wall. The present findings support the conclusion that pica in rats is analogous to vomiting in other species and suggest that pica in rats is mediated by the same mechanisms as vomiting in humans. Accordingly, we extended the utility of the animal model to pharmacological research of emesis with pica as an analogue to emesis.

Pica in rats is analogous to emesis: an animal model in emesis research.

Risks and benefits of copper in light of new insights of copper homeostasis.

Nausea and vomiting are amongst the most common symptoms encountered in medicine as either symptoms of diseases or side effects of treatments. In a more biological setting they are also important components of an organism's defences against ingested toxins. Identification of treatments for nausea and vomiting and reduction of emetic liability of new therapies has largely relied on the use of animal models, and although such models have proven invaluable in identification of the anti-emetic effects of both 5-hydroxytryptamine 3 and neurokinin 1 receptor antagonists selection of appropriate models is still a matter of debate. The present paper focuses on a number of controversial issues and gaps in our knowledge in the study of the physiology of nausea and vomiting including: The choice of species for the study of emesis and the underlying behavioural (e.g. neophobia), anatomical (e.g. elongated, narrow abdominal oesophagus with reduced ability to shorten) and physiological (e.g. brainstem circuitry) mechanisms that explain the lack of a vomiting reflex in certain species (e.g. rats); The choice of response to measure (emesis[retching and vomiting], conditioned flavour avoidance or aversion, ingestion of clay[pica], plasma hormone levels[e.g. vasopressin], gastric dysrhythmias) and the relationship of these responses to those observed in humans and especially to the sensation of nausea; The stimulus coding of nausea and emesis by abdominal visceral afferents and especially the vagus—how do the afferents encode information for normal postprandial sensations, nausea and finally vomiting?; Understanding the central processing of signals for nausea and vomiting is particularly problematic in the light of observations that vomiting is more readily amenable to pharmacological treatment than is nausea, despite the assumption that nausea represents “low” intensity activation of pathways that can evoke vomiting when stimulated more intensely.

Signals for nausea and emesis: Implications for models of upper gastrointestinal diseases

Physiological basis and pharmacology of motion sickness: an update.

The present study was aimed at evaluating quantitatively gamma-aminobutyric acid (GABA) immunoreactivity in the hindlimb representation of the rat somatosensory cortex after 14 days of hindlimb unloading by tail suspension. A reduction in the number of GABA-immunoreactive cells with respect to the control animals was observed in layer Va and Vb. GABA-containing terminals were also reduced in the same layers, particularly those terminals surrounding the soma and apical dendrites of pyramidal cells in layer Vb. On the basis of previous morphological and behavioral studies of the neuromuscular system of hindlimb-suspended animals, it is suggested that the unloading due to hindlimb suspension alters afferent signaling and feedback information from intramuscular receptors to the cerebral cortex due to modifications in the reflex organization of hindlimb muscle groups. We propose that the reduction in immunoreactivity of local circuit GABAergic neurons and terminals is an expression of changes in their modulatory activity to compensate for the alterations in the afferent information.

Quantitative changes of GABA-immunoreactive cells in the hindlimb representation of the rat somatosensory cortex after 14-day hindlimb unloading by tail suspension.

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 was produced and some animals vomited. These findings confirm other studies indicating motion can produce vomiting in animals with the area postrema destroyed and demonstrate that motion-induced 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.

/pdf/conditioned-taste-aversion-and-motion-sickness-in-cats-and-4k3efs5sb7.pdf

Conditioned taste aversion and motion sickness in cats and squirrel monkeys.

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.

Robert A. Fox

Papers

Quantitative changes of GABA-immunoreactive cells in the hindlimb representation of the rat somatosensory cortex after 14-day hindlimb unloading by tail suspension.

Conditioned taste aversion and motion sickness in cats and squirrel monkeys.

Vasopressin and motion sickness in cats.

Light microscopic image analysis system to quantify immunoreactive terminal area apposed to nerve cells.

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