Longitudinal Multiparametric Magnetic Resonance Imaging of Outbred Rats with Variable Vulnerability to the Development of Oxycodone Addiction-like Behaviors

PROJECT SUMMARY/ABSTRACT
Advancements in neuroscience, including magnetic resonance imaging (MRI), have significantly improved our
understanding of opioid use disorder (OUD) and brain function, yet due to the heterogeneity in the disorder and
complexity of the brain, controlled comprehensive approaches in heterogeneous populations are a necessity to
characterize individual variability. Here, longitudinal multi-parametric MRI is proposed to assess brain features
associated with OUD in genetically heterogeneous stock rats sourced from the NIDA-funded Rat Oxycodone
Biobank (U01DA051937), which provides rats with fully characterized genome and addiction-like behaviors,
going through a state-of-the-art pipeline with escalation of oxycodone intake following extended access to
intravenous oxycodone self-administration.
Leveraging features from structural, diffusion, and functional MRI, our investigation seeks to capture the
individual differences in the brain, at baseline before oxycodone exposure (Aim 1: pre-existing), and following
the oxycodone extended self-administration paradigm during acute withdrawal (12 h) (Aim 2: oxycodone-
induced), within the same rats that show vulnerability or resilience to developing oxycodone addiction-like
behaviors. We hypothesize that there will be an interaction between the results from both aims.
The I/START R03 proposal will allow for the introduction of MRI imaging into the PARC research environment,
as a for the PI new, clinically relevant approach, which will complement her current preclinical work with single-
cell whole-brain imaging and simplify the translation of the findings for human applications. The collaborative
pilot with the Rat Oxycodone Biobank thus aims to set up the basis for larger follow-up studies that will allow
for the generation of a heterogeneous, high-quality imaging dataset that will be made publicly available and
complement already extensive genomic and behavioral characterization in the same animals. This data will
significantly contribute to our understanding of the variable impact of opioids on the brain and individual
differences in vulnerability to OUD, providing a unique opportunity to disentangle pre-existing differences from
those that are a consequence of exposure to oxycodone. Ultimately, this research seeks to pave the way for
improved prevention and personalized treatment strategies, thereby reducing illness and disability associated
with OUD.

Grant Number: 1R03DA064666-01
NIH Institute/Center: NIH
Principal Investigator: Lieselot Carrette