Many people might experience nausea by motion sickness, hangover and so on. Such nausea and vomiting can be prevented and be patient by our behaviors. However, nausea by anti-cancer drugs is severe to lower doses of the drugs or stop their administrations and the nausea itself should be medically treated. Actually serotonin-3 (5-HT3) receptor antagonists are developed and clinically used as anti-emetic drugs but their effects on emesis occurred at a long time after the chemotherapy administration, delayed emesis, are not enough and further potent drugs are needed. Although animal experiments are essential for screening and evaluation of drugs, emetic or anti-emetic effects cannot be studied by vomiting in mice and rats because they do not vomit. We can evaluate emesis in vomiting animals such as suncus, ferrets (1), and dogs but we have a few experiences of studies in suncus and ferrets and dogs are less easy to treat due to their larger bodies than mice and rats. A pica behavior (kaolin intake) is focused as a substitute for the vomiting behavior.

6-1 Pica Behavior

An intake behavior of non-nutrients and non-food is called as a pica behavior. If this behavior is continuously observed over 1 month, it is one of eating disorders of infancy and early childhood called as pica. Diagnostic criteria for pica in DSM-IV (Diagnostic and Standard Manual of Mental Disorders Fourth Edition, The American Psychiatric Association) are following 4 items: A. eating non-nutrients continues for at least 1 month, B. eating non-nutrients is not appropriate in a developmental point of view, C. eating non-nutrients is not an acceptable custom in a cultural point of view, D. eating non-nutrients is remarkable to need a clinical intervention when this behavior is observed only during a course of the other mental disorders (e.g. mental retardation, pervasive developmental disorder, schizophrenia). Pica is different from parageusia in which we feel a different taste in a taste disorder.

6-2 Kaolin Intake

Kaolin is clay consisting of hydrated aluminum silicate. This name originates from a production area, Kaoling in Jiangxi province, China and mineral including kaolin is called as kaolinite. Because commercially available kaolin is powder and not easy to treat, we mix it with ca. 3% gum arabic and form into a pellet to use, which is a cylindrical shape like common solid foods used to rear rats and mice. A kaolin intake is observed after chemotherapy administration or X-ray irradiation in rats and mice, which is thought to induce nausea and vomiting. The kaolin intake correlates with doses of the drugs and the irradiation (2) and is also suppressed by anti-emetic drugs. Thus, the kaolin intake is known as a behavior substituting nausea and vomiting in rats and mice. The kaolin intake may suppress visceral sick sensation, which is thought to be a purposive behavior and may not become a model of pica as a mental disorder. However, we call it pica and measure the kaolin intake as a behavior taking non-nutrients.

6-2-1 Measurement of Kaolin Intake

Normal solid foods for breeding and kaolin pellets solidified with gum arabic are put into each food container and supplied to rats. We weigh each container once a day at the same time and measure their daily intakes. In this case we must collect spillages in a rearing cage and subtract their weight from the intake. Therefore, we breed rats in a mesh-floor cage without nesting materials such as paper tips and collect the kaolin or the foods separately from feces and urine.

You may expect a similar method in mice. However, we cannot evaluate it in mice because relatively more spillage compared to the less intake of kaolin than in rats and powders formed from the kaolin pellets make difficult us the separate collection from feces and urine. There is a substituting method in mice, in which we supply solid pigmented kaolin to mice, extract the pigment from feces collected and measure its absorbance as the kaolin intake (2).

6-2-2 Automatic Measurement Device in Rats

We can measure the kaolin intake by a commercially available automatic food intake monitor. It has two weight sensors and can simultaneously measure weights of food intake and kaolin intake separately. A time course of the intake can be measured in this device different from manual measurement once a day and the time course of nausea and vomiting can be evaluated (3). A special structure of this device enables that spillages fall into a spillage container under a food container and are not brought into a cage, and we can weigh residues with spillages. The device for mice with the similar structure is available as a food intake monitor. However, we cannot use it to measure the kaolin intake because we cannot ignore spillages brought into the cage due to less intake of kaolin described above.

6-3 Closing

The kaolin intake in rats is an apparently different behavior from vomiting and we do not know whether they feel nausea and emetic sensation or not. However, the behavior that clinically emetic drugs increase and anti-emetic drugs suppress the kaolin intake becomes a highly useful model to evaluate the drugs. If we find that an animal behavior apparently different from human and develop it to the useful animal model, it may be one of our pleasure in behavioral pharmacology.