Geophagia, a form of pica (ingestion of non-nutritive substances), is common in many species and has been prevalent throughout human history [1
]. Although also commonly associated with aberrant behavior leading to toxicity-related disease, e.g., lead poisoning [4
], medicinal treatment properties of geophagia have been reported in historical literature for more than 1000 years [2
]. Several explanations for geophagia have been offered. Under some circumstances, ingestion may provide scarce micronutrients such as iron or calcium [6
]. Clay may also alter gastrointestinal transit and absorption, or serve to bind or dilute a toxin in the gastrointestinal tract, thus reducing its adverse effects [8
]. In human societies, culture may also determine whether and when clay is consumed [11
Geophagia is not always adaptive. Hooper and Mann postulated that pica can be at first advantageous, but continued ingestion of clay or earth may lead to prolonged malaborption of essential nutrients, that render pica as self-propagating and unnecessarily harmful (see [13
] for discussion). For example, rats fed a maintenance diet mixed with kaolin, before and during pregnancy, had decreased hematocrit and hemoglobin levels as well as diminished red blood cell counts and low birth weight in pups [14
]. However, this paradigm may not be relevant because rats were forced to consume kaolin to get energy, which is unlike the method used here, where rats could choose kaolin alone, independent of an energy source.
The anti-neoplastic agent cisplatin, a common chemotherapy agent, exerts its cytotoxic effects primarily through direct interference with DNA synthesis, replication, or repair [see [15
] for review]. Cisplatin has many deleterious side effects including the stimulation of nausea, vomiting, anorexia and behaviors indicative of malaise [16
]. The source of emesis induced by cisplatin appears to stem from the release of serotonin from enterochromaffin cells that activates vagal afferent fibers containing 5-HT3
receptors [see [18
] for review], yet the specific neurobiological systems responsible for how this drug generates nausea and anorexia are for the most part undefined.
Intake of kaolin clay has been used as a marker for illness from a wide variety of stimuli, including cisplatin [19
]. In the rat, kaolin intake has been used as a proxy for emesis [20
] since this species does not vomit. Similar to the action of cisplatin on emesis, cisplatin-induced kaolin consumption in the rat is largely dependent on an intact gastrointestinal vagus [22
] and is inhibited by common anti-emetic drugs, such as 5-HT3
receptor antagonists, as well as corticosteroids [20
]. However, it is unknown whether the appearance of pica induced by malaise is merely an indicator of illness, or if the behavior also has an ameliorative effect to improve the welfare of the animal. Therefore, in the current study we examined whether access to kaolin influenced recovery from cisplatin-induced illness, using changes in body weight, food intake and water intake as indicators of sickness. If kaolin access is effective for reducing illness, as indicated by these measures, it implies that kaolin consumption might have therapeutic benefits.
In a previous report, access to kaolin did not influence daily food intake or body weight gain of rats that were treated weekly with a low (1 mg/kg) dose of cisplatin [21
]. This caused small and transient reductions in food intake such that recovery to baseline levels occurred within 1 or 2 days, and so was not conducive for observing kaolin-related influences on recovery. Our study used a single dose of cisplatin (6 mg/kg) that consistently produces prolonged reductions in body weight and food intake [19