Models & Assays
Evaluation of Malaise
NCEs may reduce feeding behaviour by non-specific means such as malaise. Transpharmation offer a variety of techniques to study malaise in rats, including measurement of pica, certain spontaneous behaviours and conditioned behaviours such as place aversion and conditioned disgust. Nausea and vomiting are one of the primary dose limiting side effects of CNS drugs in the clinic. Certain drug classes such as PDE4 inhibitors, e.g rolipram are associated with induction of nausea in humans.
Effect of rolipram (0.3 – 1 mg/kg) pretreatment on various measures which may reflect malaise in rats. Rolipram produced a dose related incidence of checked signs such as chin rubbing, flat body posture and chewing. These were aggregated to give a ‘malaise score’. In a separate experiment, equivalent doses of rolipram increased the amount of clay eaten over a 4h time period. Rolipram (1 mg/kg) also produced a significant place aversion for a distinct compartment it was paired to (unbiased procedure).