Department of Behavioral Science, University of Kentucky, Lexington, KY 40502, USA.
Exp Clin Psychopharmacol. 2012 Aug;20(4):310-7. doi: 10.1037/a0028327. Epub 2012 Jun 11.
Oxycodone, an opioid with known abuse liability, is misused by the intranasal route. Our objective was to develop a model of intranasal oxycodone self-administration useful for assessing the relative reinforcing effects of opioids and potential pharmacotherapies for opioid use disorders. Healthy, sporadic intranasal opioid abusers (n = 8; 7 M, 1 F) completed this inpatient 2.5-week, randomized, double-blind, placebo-controlled, crossover study. Each intranasal oxycodone dose (0, 14 & 28 mg) was tested in a separate 3-day block of sessions. The first day of each block was a sample session in which the test dose was given. Two randomized progressive ratio sessions were conducted on the next 2 days: (1) subjects could work for the test dose over 7 trials (1/7th of total dose/trial), and (2) subjects could work for either a portion of the dose (1/7th) or money ($3) over 7 trials. Physiological and subjective measures were collected before and after drug administration for all sessions. Subjects never worked to self-administer placebo regardless of whether money was available. In both self-administration sessions, oxycodone self-administration was dose-dependent. Subjects worked less for drug (28 mg oxycodone) when money was available but only modestly so. Oxycodone dose-dependently increased VAS ratings of positive drug effects (e.g., "like") during sample sessions (p < .05). These reports were positively correlated with self-administration behavior (e.g., "like," r = .65). These data suggest that both procedures are sensitive for detecting the reinforcing properties of intranasal oxycodone and may be used to further explore the characteristics of opioid compounds and potential pharmacotherapies for treatment.
羟考酮是一种具有已知滥用倾向的阿片类药物,通过鼻内途径被滥用。我们的目标是开发一种用于评估阿片类药物相对强化作用和治疗阿片类药物使用障碍的潜在药物治疗的鼻内羟考酮自我给药模型。健康、偶发鼻内阿片类药物滥用者(n = 8;7 名男性,1 名女性)完成了这项为期 2.5 周的住院、随机、双盲、安慰剂对照、交叉研究。在单独的 3 天疗程块中测试了每个鼻内羟考酮剂量(0、14 和 28 mg)。每个块的第一天是进行测试剂量的样本疗程。在接下来的 2 天中进行了 2 个随机递增比例疗程:(1)受试者可以在 7 次试验中争取测试剂量(每次试验为总剂量的 1/7),(2)受试者可以在 7 次试验中争取部分剂量(1/7)或金钱($3)。在所有疗程中,给药前后都收集了生理和主观测量值。无论是否有金钱可用,受试者都不会自行服用安慰剂。在两种自我给药疗程中,羟考酮的自我给药均呈剂量依赖性。当有金钱可用时,受试者为药物(28 mg 羟考酮)工作的次数减少,但只是适度减少。在样本疗程中,羟考酮剂量依赖性地增加了 VAS 对积极药物作用的评分(例如,“喜欢”)(p <.05)。这些报告与自我给药行为呈正相关(例如,“喜欢”,r =.65)。这些数据表明,这两种程序都能灵敏地检测鼻内羟考酮的强化特性,并且可能用于进一步探索阿片类化合物的特性和治疗的潜在药物治疗。