Behavioral Mechanisms of Oxycodone's Effects in Female and Male Rats: Reinforcement Delay and Impulsive Choice

• Published in: Experimental and clinical psychopharmacology 2023-12, Vol.31 (6), p.1050-1068
• Main Authors: Blejewski, Ryan C., Van Heukelom, Justin T., Langford, Jeremy S., Hunt, Katelyn H., Rinkert, Isabelle R., Wagner, Thomas J., Pitts, Raymond C., Hughes, Christine E.
• Format: Article
• Language: English
• Subjects: Analgesics, Opioid - pharmacology; Animal; Animal Sex Differences; Animals; Choice Behavior; Conditioning, Operant; Delay Discounting; Female; Impulsive Behavior; Impulsiveness; Male; Male Animals; Opioid Analgesics; Oxycodone; Oxycodone - pharmacology; Rats; Reinforcement Delay; Reinforcement, Psychology
• ISSN: 1064-1297; 1936-2293; 1936-2293
• DOI: 10.1037/pha0000646

μ-Opioid agonists (e.g., morphine) typically increase impulsive choice, which has been interpreted as an opioid-induced increase in sensitivity to reinforcement delay. Relatively little research has been done with opioids other than morphine (e.g., oxycodone), or on sex differences in opioid effects, on impulsive choice. The present study investigated the effects of acute (0.1-1.0 mg/kg) and chronic (1.0 mg/kg twice/day) administration of oxycodone on choice controlled by reinforcement delay, a primary mechanism implicated in impulsive choice, in female and male rats. Rats responded under a concurrent-chains procedure designed to quantify the effects of reinforcement delay on choice within each session. For both sexes, choice was sensitive to delay under this procedure. Sensitivity to delay under baseline was slightly higher for males than females, suggesting more impulsive choice with males. When given acutely, intermediate and higher doses of oxycodone decreased sensitivity to delay; this effect was larger and more reliable in males than females. When given chronically, sex differences were also observed: tolerance developed to the sensitivity-decreasing effects in females, whereas sensitization developed in males. These data suggest that reinforcement delay may play an important role in sex differences in impulsive choice, as well as in the effects of acute and chronic administration of opioids in impulsive choice. However, drug-induced changes in impulsive choice could be related to at least two potential behavioral mechanisms: reinforcement delay and/or reinforcement magnitude. Effects of oxycodone on sensitivity to reinforcement magnitude remain to be fully characterized. Public Health Significance The study presents an important preclinical evaluation of effects of opioids on a critical behavioral mechanism involved in impulsive choice, reinforcement delay. Although baseline sensitivity to delay was lower in females than males, suggesting males may be more impulsive, oxycodone produced comparable decreases in sensitivity in both sexes. Ultimately, these data may inform translational research on risk factors associated with, and negative outcomes of, substance use disorder.