2026 Undergraduate Research Showcase

Behavioral Analysis and Validation of a Morphine Dependence Mouse Model

Document Type

Student Presentation

Presentation Date

4-24-2026

Faculty Sponsor

Dr. Lauren Faget

Abstract

Understanding and quantifying opioid withdrawal symptoms is essential for validating preclinical models of dependence and advancing research on substance use disorders. Morphine dependence arises following repeated exposure, producing neuroadaptations that manifest as both somatic (physical) and affective (emotional/motivational) withdrawal symptoms upon drug cessation or receptor blockade. Distinguishing between these domains is important, as they capture different aspects of the withdrawal state. In the present study, we sought to validate a modified morphine dosing paradigm designed to balance experimental practicality with the reliable induction of opioid dependence. Mice were rendered dependent using an escalating morphine dosing regimen administered once daily over five days (20–50 mg/kg). This protocol was selected for its practicality—requiring only a single daily injection—and for maintaining a relatively low maximal dose compared to traditional paradigms, thereby enabling behavioral testing during drug exposure. Given these modifications, it was critical to confirm that this regimen still robustly induces opioid dependence. Withdrawal-related behaviors were assessed using systematic behavioral scoring across three cohorts: naloxone-precipitated withdrawal at 2 or 24 hours following the final morphine injection, and spontaneous withdrawal at 24 hours post-treatment. Saline-treated mice served as controls. To capture the full spectrum of withdrawal, we implemented two complementary global withdrawal scoring (GWS) methods: one emphasizing somatic signs (e.g., paw tremors, jumping, body tremors, piloerection, ptosis, teeth chattering), and a second incorporating both somatic and affective-related behaviors. Morphine-treated mice exhibited robust, time-dependent withdrawal symptoms, with naloxone producing pronounced effects, while spontaneous withdrawal revealed broader behavioral changes when assessed with the integrative GWS approach. These findings confirm that this modified paradigm reliably induces opioid dependence while preserving experimental flexibility.

This validated model establishes a strong foundation for future studies investigating opioid-induced neuroadaptations at the 24-hour withdrawal time point using proteomics, RNAscope-based transcriptomics, fiber photometry, and circuit connectivity mapping, providing mechanistic insight into opioid dependence.

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