PERO: A stress-free, quantitative oral administration method through voluntary licking behavior

Abstract

Oral administration is widely used in pharmacological experiments. However, the most common method, oral gavage, causes stress responses through restraint and insertion of a needle into the stomach, often affecting subsequent animal behaviors such as sleep/wake. Here, we developed a new method of voluntary oral administration: PERO. In PERO, we used a mixture of viscous paste foods (e.g. sweetened condensed milk) and a solvent (dimethyl sulfoxide) as vehicle. Mice rapidly and completely consumed the vehicle by licking, and the behavior persisted for 4 weeks when repeated daily. Plasma corticosterone levels showed that our method was significantly less stressful than oral gavage. Moreover, we demonstrated the utility of the method through an assay for sleep-inducing effects of a water-insoluble orexin antagonist. In conclusion, PERO will be useful especially in behavioral neuroscience vulnerable to stress responses, and will improve animal welfare.