(762.10) State-dependent breathing emerges from interactions between repeated opioid use (ROU) and context

Poster Board Number: E537

Caroline Szujewski (University of Chicago), Wesley Wang (Ohio State University), Jose Otero (Ohio State University), Alfredo Garcia III (University of Chicago)

ROU is arguably the single-most influential factor driving respiratory-related morbidities, overdose, and overdose-related deaths in the ongoing opioid epidemic.  When ROU is paired with the same environmental context (i.e., the drug-paired context), it can produce pharmacodynamic tolerance to overdose-related deaths. However, it is not clear if this context-dependent tolerance impacts opioid induced respiratory depression (OIRD). This ongoing work examines how context pairing with ROU impacts breathing and OIRD. We developed a mouse model of ROU where five days of fentanyl administration (0.7 mg/kg) is paired with the same context. On subsequent testing days, OIRD in the fentanyl-paired context (FP) was compared to OIRD in a novel environment. In the majority of mice (n=7 of 11), OIRD in the FP was smaller when compared to OIRD in the novel environment. Additionally, unsupervised machine learning of breathing metrics revealed that breathing patterns following ROU is distinct in FP as compared to that in the novel environment. These results indicate that behavior related to ROU impacts the consequence of opioids on breathing and produces predictable forms of state-dependent breathing. Our findings may be leveraged to better predict and/or mitigate the occurrence of overdose-related deaths associated with ROU.

T32DA043469