Applicability of the micropipette-guided drug administration (MDA) method for assessing reward-related behaviors in mice

Oral gavage is the standard method for acute or chronic per os treatments in laboratory rodents. It can, however, induce significant stress responses and compromise the welfare of animals. To mitigate these concerns, we recently introduced the micropipette-guided drug administration (MDA) method, which utilizes a palatable vehicle (diluted sweetened condensed milk) for voluntary ingestion of drug solutions. While MDA minimizes stress and potential injury, the sugar content of the vehicle raises concerns about its possible influence on reward-related behaviors.. This study examined whether acute or chronic exposure to the MDA vehicle affects the performance of male and female C57BL/6 mice in three behavioral tests that are commonly used to assess reward-related functions, namely the novelty-suppressed eating, sucrose preference, and incentive runway tests. Compared to corresponding sham handling, neither acute nor chronic exposure to the MDA vehicle affected novelty-suppressed eating or sucrose preference in either sex. However, chronic but not acute exposure to the MDA vehicle influenced the animals' performance in the incentive runway test, with a significant effect observed in male mice specifically. This sex-dependent outcome suggests that male mice may be more susceptible to changes in reward-seeking behavior after chronic exposure to the MDA vehicle. In conclusion, our findings support the suitability of the MDA method for studies utilizing the novelty-suppressed eating and sucrose preference tests, while highlighting the need for careful consideration when assessing reward-seeking behavior in male mice using the incentive runway test.