Behavioral mechanisms of oxycodone's effects in female and male rats: Reinforcement delay and impulsive choice.

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. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Effects of oxycodone on sensitivity to reinforcement magnitude: implications for effects of opioids on impulsive and risky choice.

Opioid addiction/dependence is associated with impulsive and risky behavior. Moreover, opioids can increase impulsive choice in preclinical studies with nonhumans. The objective of this study was to investigate a potential behavioral mechanism of opioids: a change in the impact of reinforcement magnitude on choice. Rats (n = 7) chose between smaller and larger reinforcers under a continuous-choice (concurrent-chains) procedure. The levers associated with the smaller and larger reinforcers alternated every five sessions. During baseline under this procedure, rats showed a reliable preference for the larger reinforcer. Effects of several doses (0.1-1.7 mg/kg, s.c.) of the prescription opioid, oxycodone, were examined on preference based upon reinforcement magnitude. Oxycodone dose-dependently decreased preference for the larger reinforcer (i.e. decreased sensitivity to reinforcement magnitude). The decrease in sensitivity to reinforcement magnitude was selective in that the intermediate doses did not affect, or had minimal impact on, other measures of performance (e.g. on general motivation to respond). These data suggest that a decrease in the sensitivity to reinforcement magnitude is a reliable outcome of µ-opioid administration, an effect that has important implications for the impact of these drugs on both impulsive and risky behavior.