Blejewski Ryan C, Van Heukelom Justin T, Vidal Pedro, Hughes Christine E, Pitts Raymond C
Department of Psychology, University of North Carolina Wilmington, Wilmington, North Carolina; Pediatric Psychology, Center for Pediatric Behavioral Health, Wilmington, North Carolina.
Department of Psychology, University of North Carolina Wilmington, Wilmington, North Carolina; Department of Health Education & Behavior and Center for Behavioral Economic Health Research, University of Florida, Gainesville, Florida.
J Pharmacol Exp Ther. 2025 Aug;392(8):103648. doi: 10.1016/j.jpet.2025.103648. Epub 2025 Jun 30.
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.
冲动选择在经验上可定义为,在涉及不同强化量值和延迟的选择中,偏好较小且较早的强化物而非较大且较晚的强化物。阿片类激动剂会增加冲动选择;然而,除吗啡外的其他阿片类药物尚未得到广泛研究。本研究的目的是通过表征其对雌性(n = 6)和雄性(n = 8)大鼠强化量值和延迟的相对影响,来研究处方阿片类药物羟考酮对冲动选择的急性影响。研究假设羟考酮会降低对量值和延迟的敏感性。大鼠在并发链程序下做出反应,在此程序中,量值和延迟的组合在实验过程中进行操纵。一个选项的量值和延迟组合在整个实验中保持不变,而另一个选项的组合在实验过程中变化。对于两性而言,选择受量值和延迟的综合影响控制;平均而言,对量值的敏感性高于对延迟的敏感性。羟考酮降低了两性对量值和延迟的敏感性,相对于延迟,对量值的敏感性降低幅度更大,这表明羟考酮可能通过降低对量值的敏感性大于对延迟的敏感性来增加冲动选择。然而,这些影响在不同大鼠之间存在差异。进一步分析表明,羟考酮对量值和延迟敏感性的影响是其对各个杠杆反应的速率依赖性影响的结果。这些数据说明了彼得·杜斯对理解药物行为效应的持久贡献。意义声明:阿片类药物使用障碍与冲动和危险行为的可能性增加有关。本研究在冲动选择的临床前啮齿动物模型中研究了处方阿片类药物羟考酮作用的行为机制。在此程序下,羟考酮的作用是速率依赖性的,这一发现可能对包括阿片类药物使用在内的冲动障碍治疗具有重要意义,并且说明了彼得·杜斯对行为药理学的持久贡献。