Sex and strain differences in the micropipette-guided drug administration (MDA) method in mice

To provide an alternative to oral gavage for per os treatments in laboratory mice, we have recently developed and introduced the micropipette-guided drug administration (MDA) method. This procedure is based on the presentation of a palatable solution consisting of sweetened condensed milk diluted with water, encouraging voluntary consumption of the vehicle and drug formulations. In this study, we compared the MDA method in male and female C57BL/6N and BALB/c mice, two inbred strains widely used in basic and preclinical research. Administering a diluted condensed milk solution daily over a period of 30 days, we observed that male C57BL/6N mice reached the fully voluntary drinking stage within five days or less, requiring the least amount of time to drink from the micropipette. Compared with males, female C57BL/6N mice showed increased consumption times during the initial administration period, yet they all managed to reach a fully voluntary stage within seven days or less. By contrast, BALB/c mice in general, and female BALB/c mice in particular, consistently required more time to consume the diluted condensed milk solution, whether administered voluntarily (no restraint) or semi-voluntarily (with mild tail restraint). Notably, a substantial portion of BALB/c mice (12.5% of males and 62.5% of females) failed to achieve fully voluntary consumption by MDA, despite their ability and willingness to drink the condensed milk solution when using a mild tail restraint. Taken together, the present study identified significant strain and sex differences in the MDA method as applied to laboratory mice.