Disruptions in Reward-Guided Decision-Making Functions Are Predictive of Greater Oral Oxycodone Self-Administration in Male and Female Rats

Abstract

Background

Problematic opioid use that emerges in a subset of individuals may be due to preexisting disruptions in the biobehavioral mechanisms that regulate drug use. The identity of these mechanisms is not known, but emerging evidence suggests that suboptimal decision making that is observable prior to drug use may contribute to the pathology of addiction.

Methods

The current study investigated the relationship between decision-making phenotypes and opioid-taking behaviors in male and female Long Evans rats. Adaptive decision-making processes were assessed using a probabilistic reversal learning task and oxycodone- (or vehicle, as a control) taking behaviors assessed daily in 32 sessions using a saccharin fading procedure that promoted dynamic intake of oxycodone. Tests of motivation, extinction, and reinstatement were also performed.

Results

Computational analyses of decision-making data identified data-driven metrics that predicted self-administration of oxycodone and addiction-relevant behaviors. Moreover, preexisting impairments in reward-guided decision making observed in female rats were associated with greater addiction-relevant behaviors when compared with males.

Conclusions

These results provide new insights into the biobehavioral mechanisms that regulate opiate-taking behaviors and offer a novel phenotypic approach for interrogating sex differences in addiction susceptibility and opioid use disorders.