The relationship between duration of access to intravenous oxycodone self-administration, economic demand for oxycodone, and cognition in rats

Rationale: Individuals who use opioids display cognitive deficits. Objectives: Here we used oxycodone intravenous self-administration (IVSA) to test the hypothesis that cognitive deficits would be observed in rats following opioid exposure and would worsen with increased oxycodone-seeking. Methods: Male and female Sprague-Dawley rats were trained to self-administer oxycodone or food. Rats either underwent short-access (ShA; 3 hr/day) or long-access (LgA; 6 hr/day) oxycodone IVSA. Control rats underwent 3 hr/day food self-administration. Next, rats underwent economic demand analysis wherein the number of responses required to obtain a reinforcer was increased. After 14 days of abstinence, rats were tested for cue-primed relapse of reinforcer-seeking. Rats then underwent novel object recognition (NOR) testing followed by assessment of cognitive flexibility using the probabilistic reversal learning (PRL) task. Rats were perfused following the last PRL session for assessment of cortical activity via c-fos immunohistochemistry. Results: While LgA rats had greater oxycodone intake, there were no effects of access length on demand elasticity or cued seeking. Modest effects of oxycodone exposure were found on cognition, including increased NOR performance in LgA rats and different PRL strategies. Despite equivalent behavior shown during the final PRL session, ShA rats displayed increased c-fos expression in the orbitofrontal cortex (OFC). Conclusions: While oxycodone self-administration does not overtly impair PRL performance, more activity in the OFC is necessary to maintain the same level of performance. Furthermore, length of daily oxycodone access is not a determinant of economic demand for oxycodone.