BN Kuhn1 (presenting author underlined)

The rise of opioid use disorder (OUD) worldwide makes it imperative to disentangle the behavioral, genetic and neurobiological correlates associated with both OUD vulnerability and resiliency. Using a novel preclinical rat model of OUD that captures the multi-symptomatic diagnosis and complex multidimensional interactions between symptoms conferring OUD propensity, we have shown distinct behavioral and neurobiological profiles associated with each phenotype (n>1000). Additionally, genome-wide association study (GWAS; n=874) analysis indicates both resiliency and vulnerability to OUD are heritable states. GWAS identified genetic variants for nociception, heroin consumption and motivation to obtain heroin, with OUD vulnerability associated with the latter two. Several of the identified genes are known regulators of neuroplasticity, thereby prompting further investigation into neuroplastic mechanisms contributing to OUD propensity. Guided by findings from GWAS, we are assessing OUD phenotypic differences in components of the extracellular matrix (ECM), microglia and dendritic spine morphology within a canonical circuit necessary for OUD-like behaviors (prelimbic cortex, PrL; nucleus accumbens core, NAc; ventral pallidum, VP). Opposing phenotypic differences in PrL and VP ECM and microglia plasticity are evident, suggesting a mechanistic role for these neuroplastic components in mediating OUD vulnerability and resiliency. Furthermore, cell-specific alterations in NAc dendritic spine morphology are currently underway. Together these data identify novel genetic loci associated with OUD behaviors and vulnerability which further guided the assessment into neuroplastic measures that are likely contributing to OUD vulnerability and resiliency.

¹Department of Psychology and Neuroscience, Baylor University, Waco, TX, USA