Behavioral mechanisms of oxycodone's effects in female and male rats: Rate-dependent effects on impulsive choice.

Abstract

Impulsive choice may be empirically defined as a preference for a smaller-sooner reinforcer over a larger-later reinforcer with choices involving different reinforcement magnitudes and delays. Opioid agonists increase impulsive choice; however, opioids other than morphine have not been examined extensively. The aim of the current study was to examine the acute effects of the prescription opioid oxycodone on impulsive choice by characterizing its effects on the relative impact of reinforcement magnitude and delay in female (n = 6) and male (n = 8) rats. It was hypothesized that oxycodone would decrease sensitivity to both magnitude and delay. Rats responded under a concurrent-chains procedure in which combinations of magnitude and delay were manipulated within sessions. The combination of magnitude and delay for one option was constant across the experiment, whereas the combination for the other option was varied within the session. For both sexes, choice was controlled by the combined effects of magnitude and delay; on average, sensitivity to magnitude was higher than to delay. Oxycodone decreased sensitivity to magnitude and delay in both sexes, with a greater reduction in sensitivity to magnitude relative to delay, suggesting oxycodone may increase impulsive choice by decreasing sensitivity to magnitude more than sensitivity to delay. These effects, however, varied across rats. Additional analyses indicated that oxycodone's effects on sensitivity to both magnitude and delay were an outcome of rate-dependent effects on responding on the individual levers. These data illustrate the enduring contributions of Peter Dews to the understanding of behavioral effects of drugs. SIGNIFICANCE STATEMENT: Opioid use disorder is associated with an increased likelihood of impulsive and risky behaviors. This study investigated the behavioral mechanisms of the effects of the prescription opioid, oxycodone, in a preclinical rodent model of impulsive choice. Effects of oxycodone under this procedure were rate-dependent, a finding that may have important implications for the treatment of impulsive disorders, including opioid use, and one that illustrates the enduring contributions of Peter Dews to behavioral pharmacology.