Self-Administration of Drugs in Mouse Models of Feeding and Obesity
June 8th, 2021
The overall goal of this procedure is to describe a method for self-administration of drugs that can be used 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.
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Overview
This article describes a method for self-administration of drugs in mouse models, specifically targeting feeding and obesity research. By using palatable food, such as peanut butter, researchers can minimize stress associated with traditional drug delivery methods.
Key Study Components
Area of Science
- Neuroscience
- Pharmacology
- Obesity Research
Background
- Traditional drug delivery methods can affect food intake and body weight.
- Invasive methods include injections and oral gavage.
- Self-administration can reduce stress in animal models.
- Using palatable food can enhance drug acceptance by mice.
Purpose of Study
- To develop a less invasive method for drug administration in mice.
- To facilitate research on feeding behaviors and obesity.
- To improve the welfare of animal subjects during experiments.
Methods Used
- Pulverizing drug tablets using a mortar and pestle.
- Weighing peanut butter on a tared scale.
- Melted peanut butter is mixed with the pulverized drug.
- The mixture is cooled and placed into a mold for self-administration.
Main Results
- The method allows for self-administration with minimal stress.
- Mice can consume the drug mixed with food at their own pace.
- This approach may lead to more accurate behavioral assessments.
- It opens new avenues for studying drug effects on feeding and obesity.
Conclusions
- Self-administration using palatable food is effective in mice.
- This method can enhance the validity of preclinical studies.
- Future research can build on this technique for various compounds.
Frequently Asked Questions
Executive Industry Relevance
Stress from invasive drug delivery methods can confound metabolic endpoints in obesity and feeding studies, reducing data reliability. Self-administration via palatable food minimizes procedural stress, improving translational relevance for chronic dosing regimens. This approach supports more accurate assessment of drug effects on food intake and body weight in preclinical models.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Scientific Value: Enables interrogation of therapeutic hypotheses related to feeding behavior and metabolic regulation with reduced confounding from administration stress.
- Operational Value: Provides a reproducible, low-stress method for chronic compound delivery in mouse models.
Screening & Assay Development
- Scientific Value: Generates consistent oral exposure profiles suitable for dose-response characterization in metabolic phenotyping assays.
- Operational Value: Supports standardized preparation of drug-food matrices for high-throughput evaluation of candidate compounds.
Translational & Preclinical Research
- Scientific Value: Aligns with clinical dosing patterns by enabling voluntary, timed intake, enhancing predictive confidence in obesity therapeutics.
- Operational Value: Facilitates studies on circadian timing of drug administration and its impact on metabolic outcomes.
Pipeline & Workflow Integration
This method fits within the discovery continuum from target validation through preclinical evaluation, particularly for compounds affecting feeding, energy balance, and obesity-related pathways.
- Discovery Biology: Supports hypothesis testing on drug effects on food intake and weight gain by minimizing stress-induced artifacts.
- Screening: Enables standardized, voluntary oral delivery for consistent compound exposure in feeding behavior assays.
- Analytics: Generates quantifiable endpoints such as daily food intake and body weight change for comparative analysis.
- Translational Research: Models clinical-relevant dosing schedules to study circadian influences on drug efficacy and metabolic health.
- Enterprise Reuse: Represents a scalable, adaptable platform for chronic oral delivery across multiple therapeutic areas in metabolism research.
Operational & Enterprise Impact
- Scientific Value: Reduces mechanistic ambiguity by isolating drug effects from stress-related metabolic perturbations.
- Operational Value: Improves reproducibility and animal welfare through non-invasive, voluntary administration.
- Strategic Value: Enhances go/no-go decision confidence by providing cleaner phenotypic data in obesity models.
- Portfolio Impact: Enables risk-adjusted prioritization of compounds based on reliable metabolic readouts.
Implementation Considerations
- Expertise in formulation science to ensure drug stability and homogeneity in peanut butter matrix.
- Access to precision weighing and mixing equipment for accurate dosing.
- Standardized training protocols to ensure consistent pellet consumption across study groups.
- Consideration of food intake timing and circadian factors when designing dosing schedules.
- Limitations include potential variability in intake based on palatability and satiety, requiring monitoring of actual drug exposure.
