Unmasking Convergent Oxycodone Seeking and Consumption Driving Augmented Intake during Extended Access to Oral Operant Self-Administration.

Individual vulnerability to opioid intake escalation is a critical but poorly understood aspect of addiction. Using genetically diverse inbred rat strains, we investigated operant oral oxycodone self-administration, identifying 'Augmenter' phenotypes that dramatically increased consumption during extended (16h vs. 4h) access-a vulnerability not predicted by standard motivation tests. A key innovation was applying lick microstructure analysis (LMA) to operationally distinguish 'consumption' from 'seeking' lick clusters within the inter-reward interval. During extended access, Augmenters of both sexes exhibited a striking surge in the of both consumption and seeking clusters (p<0.0001), driving their escalated intake. Notably, female Augmenters also showed larger seeking cluster sizes (p=0.006), suggesting enhanced reward value specifically linked to seeking behavior. In contrast, interlick interval (a palatability measure) did not differentiate phenotypes. This LMA-based approach reveals that an increased drive to seek out additional oxycodone, rather than altered hedonic impact alone, underlies the augmentation of opioid intake, offering a nuanced rodent model of heightened vulnerability and a powerful tool to dissect reward dynamics.