EVALUATING GROWTH FACTORS AS BIOMARKERS FOR OPIOID USE DISORDER IN A MOUSE MODEL

The opioid crisis, driven by widespread opioid misuse, has become a major public health concern over the past three decades. Identifying molecular biomarkers for opioid use disorder (OUD) could improve diagnosis and support more personalized treatment. Preliminary evidence suggests that three growth factors – brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and fibroblast growth factor 2 (FGF2) – known to regulate drug and alcohol use disorders, may also contribute to OUD. Here, we investigated the associations between the blood and brain expression of these growth factors and opioid addiction-related behaviors in mice. To model opioid-induced behavioral adaptations, we used two paradigms, each with morphine and fentanyl: opioid-induced psychomotor sensitization, modeling drug-induced behavioral adaptations, and voluntary oral self-administration in an intermittent access two-bottle choice protocol across 6 weeks. Although the serum levels of the three growth factors did not differ between opioid- and vehicle-treated mice we found that the individual variability in these factors was strongly associated with behavioral outcomes. In both sensitization experiments, lower baseline BDNF and higher baseline FGF2 levels predicted stronger morphine- and fentanyl-induced responses, explaining 78–80% of individual variance. Additionally, GDNF and FGF2 levels measured after three weeks of morphine self-administration predicted morphine preference over water around this period. Overall, we show that serum BDNF, GDNF, and FGF2 reflect individual differences in the vulnerability for opioid-related behaviors, with predictive relevance depending on opioid type, dose, and behavioral paradigm. Together, our findings indicate the potential utility of the growth factors as biomarkers for addiction-related behaviors.