Heightened Hedonic Impact and Drug Seeking Drive the Dramatic and Heritable Augmentation of Oxycodone Intake in Rats

Abstract

Dissecting the interplay between hedonic "liking" and motivational "wanting" is key to uncovering opioid addiction mechanisms. Using genetically diverse inbred rat strains trained on an operant oral oxycodone self-administration task, we identified "Augmenter" strains showing a surge in intake during extended (16-h) access. We analyzed 562,000 lick clusters, using a novel method of lick microstructure analysis, to distinguish oxycodone consumption from seeking. Augmented intake reflected increases in the number of both consummatory and seeking clusters across sexes. In female Augmenters, strong correlations between consumption and seeking cluster size (i.e. measure of hedonic impact) and interlick interval indicated that heightened hedonic experience during consumption directly amplified motivation to seek drug; in males, this linkage was weaker. Differentiating consummatory from seeking clusters thus provides a powerful framework for parsing hedonic and motivational components of opioid use, revealing that elevated hedonic impact drives the heritable, female-biased augmentation of oxycodone intake.