Self-Administration of Drugs in Mouse Models of Feeding and Obesity

Preclinical studies in mice often rely on invasive drug delivery, such as injections or oral gavage that can have significant effects on food intake and body weight. To overcome these limitations, drugs can be mixed with highly palatable food such as peanut butter, allowing mice to self-administer compounds with minimal stress compared with an injection or a gavage. Begin by pulverizing the drug tablets in a mortar using a pestle.

Weigh the calculated amount of peanut butter in a weigh boat on a tared scale. Then, melt it over a beaker of warm water and mix the calculated amount of the pulverized drug into the melted butter. When cooled, place the peanut butter drug mix into a mold.

Prepare the placebo pellets with peanut butter alone in a similar fashion. Freeze the mold in 80 degrees Celsius to allow the peanut butter to harden until use. Prepare standard mouse cages with a lining of highly absorbent paper bedding and enrichment, including paper towels and a housing dome.

House a single mouse in each cage. Provide ad libitum food and water in the cages, and allow the mice to acclimate to the housing for approximately three days. Before starting the training, fast the mice for 24 hours.

On the next day, place a placebo peanut butter pellet as a control on the wall of the cage approximately 1.5 inches from the base. Due to novelty, it may take approximately one hour for the mouse to consume the peanut butter pellet on the first day of a trial. The chronic delivery of risperidone in peanut butter for 14 days facilitated significantly higher daily food intake and more weight gain in C57 black 6 female mice, compared with control.

Intraperitoneal delivery of risperidone in the same dosage did not have such robust effects on food intake or weight gain compared to self-delivery in peanut butter. When conducting this protocol, it is important to be consistent with the accuracy of the measurements of food intake, body weight, and the timing of drug administration throughout the study. Future application of this technique include the studies of the timing of drug delivery on food intake and weight gain in the context of circadian rhythm and metabolic health.