Department of Psychology, Slippery Rock University.
Department of Psychology, University of Kentucky.
Exp Clin Psychopharmacol. 2019 Dec;27(6):515-521. doi: 10.1037/pha0000275. Epub 2019 Mar 21.
A devastating feature of drug dependence is the susceptibility of relapse (40-60%) after stretches of abstinence. In both animal and human research, it has been demonstrated that cues (e.g., levers, paraphernalia) associated with drug reward can instigate renewed drug taking. Research has shown animals that attend to a cue that predicts reward more than the location of reward delivery when the cue is present (sign trackers) have an increase in corticosterone (CORT), a primary stress hormone when compared with animals that do not sign track. This interaction of sign tracking and CORT implicate CORT's effects as a possible pharmacological target for cue-induced relapse behaviors. PT150 is a novel glucocorticoid receptor antagonist that reduces the effects of CORT. Previous research has shown that oral administration of 40 mg/kg PT150 reduced sign tracking. To better understand dose-dependent effects and to control for more accurate doses, the current experiment hypothesized that PT150 (20/40/60 mg/kg) given by subcutaneous (SC) injection to male quail would reduce sign tracking to a keylight conditional stimulus that predicts a grain unconditioned stimulus dose dependently. Results showed that SC injection of 20 mg/kg PT150 reduced sign tracking, but 40 or 60 mg/kg did not. The main findings from the current study are that the glucocorticoid receptor antagonist PT150 reduces sign tracking behavior dose dependently, and SC administration may provide better bioavailability compared with our previous study that used an oral route of administration. The current findings support previous literature by suggesting that the glucocorticoid receptor may be a potential pharmacological target for reducing relapse-like behaviors. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
药物依赖的一个破坏性特征是在长时间禁欲后复发的易感性（40-60%）。在动物和人类研究中，已经证明与药物奖励相关的线索（例如杠杆、用具）可以引发重新吸毒。研究表明，当线索存在时，与关注预测奖励的线索相比，关注奖励传递位置的动物（标志跟踪者）的皮质酮（CORT）增加，CORT 是一种主要的应激激素。与不进行标志跟踪的动物相比。这种标志跟踪和 CORT 的相互作用表明，CORT 的作用可能是一种药物靶点，用于引发线索诱导的复发行为。PT150 是一种新型的糖皮质激素受体拮抗剂，可降低 CORT 的作用。先前的研究表明，口服给予 40mg/kgPT150 可减少标志跟踪。为了更好地了解剂量依赖性效应，并控制更准确的剂量，目前的实验假设，通过皮下（SC）注射给予雄性鹌鹑 20/40/60mg/kgPT150 将减少对预测依赖于谷物无条件刺激剂量的关键光条件刺激的标志跟踪。结果表明，SC 注射 20mg/kgPT150 可减少标志跟踪，但 40 或 60mg/kg 则不行。目前研究的主要发现是，糖皮质激素受体拮抗剂 PT150 可依赖剂量减少标志跟踪行为，与我们之前使用口服途径给药的研究相比，SC 给药可能提供更好的生物利用度。目前的研究结果支持了先前的文献，表明糖皮质激素受体可能是减少类似复发行为的潜在药理学靶点。（PsycINFO 数据库记录（c）2019APA，保留所有权利）。
