Development of Tolerance to the Dietary Plant Secondary Metabolite 1,8-cineole by the Brushtail Possum (Trichosurus Vulpecula)

The common brushtail possum (Trichosurus vulpecula) is a generalist herbivore whose diet includes Eucalyptus leaves that are well defended by plant secondary metabolites (PSM) such as the terpene 1,8-cineole (cineole). We accustomed possums to a terpene-free diet, then challenged them with the addition of 2% cineole to the diet. Initially, there was a 50% reduction in total overnight food consumption associated with a marked decrease in the mass of the major feeding bout. After nine nights, however, cineole tolerance had developed as total food consumption had returned to the control amount. Compared to the control diet, the cineole diet was eaten in a larger number of smaller bouts, which were also eaten at a slower rate. The experiment was repeated with animals that had been accustomed to day-time feeding to take blood samples during feeding sessions. Feeding variables and blood concentration data for cineole were compared on the first and seventh day of the cineole diet. Although the total food consumed increased 2.5-fold after 7 days of the cineole diet, there was no increase in average blood cineole concentration, measured as the area under the concentration-time curve. This indicates that induction of liver enzymes resulted in greater pre-systemic metabolism of cineole and reduced bioavailability. The maximum tolerated blood concentration of cineole also increased, suggesting some adaptation of the central nervous system to the cineole aversive effects. This appears to be the first report in a vertebrate herbivore that consumption of a dietary PSM leads to metabolism induction and that this contributes to development of tolerance to the PSM. Overall, herbivores adapt to newly encountered dietary PSMs by immediate changes in feeding behavior followed by development of increased metabolism of PSM and probably diminished cellular responsiveness to effects.