Department of Psychology, University of Kentucky, Lexington, KY, 40506, USA.
Psychopharmacology (Berl). 2023 Feb;240(2):295-301. doi: 10.1007/s00213-022-06299-y. Epub 2023 Jan 6.
Alcohol use disorder (AUD) has been shown to be associated with a dysregulated stress system. Reducing the stress hormone corticosterone (CORT), that binds to glucocorticoid receptors, may attenuate the rewarding properties of drugs of abuse. However, the effect of blocking corticosterone receptors on ethanol reward has yet to be investigated.
The current study investigated whether the stress hormone receptor antagonist, PT150, would block the rewarding properties of ethanol via the glucocorticoid receptor system and attenuate other ethanol-induced effects.
A conditioned place preference (CPP) procedure was used to examine the rewarding properties of ethanol in an avian preclinical model. Ethanol was paired with the least preferred chamber. On alternate days, water was paired with the preferred chamber. After eight pairings, a place preference test was given that allowed subjects to have access to both chambers. Half of the subjects received PT150 prior to ethanol administration. The other half received vehicle. Time spent in each chamber during the preference tests, locomotor activity during the pairings, and egg production in female birds was recorded.
Ethanol treatment resulted in a CPP and pretreatment of PT150 blocked the acquisition of the ethanol-induced place preference. Neither ethanol nor PT150 altered locomotor activity. Pretreatment of PT150 also increased egg production in female quail treated with ethanol.
These findings suggest repeated ethanol pairings with visual cues can produce a CPP. Furthermore, pretreatment of PT150 may be a potential pharmacotherapy for blocking the rewarding properties of ethanol and may enhance egg production in female quail treated with ethanol.
酒精使用障碍(AUD)已被证明与应激系统失调有关。减少与糖皮质激素受体结合的应激激素皮质酮(CORT)可能会减弱滥用药物的奖赏特性。然而,阻断皮质酮受体对乙醇奖赏的影响尚未得到研究。
本研究调查了应激激素受体拮抗剂 PT150 是否通过糖皮质激素受体系统阻断乙醇的奖赏特性,并减弱其他乙醇诱导的作用。
采用条件性位置偏爱(CPP)程序在禽类临床前模型中研究乙醇的奖赏特性。将乙醇与最不喜欢的室配对。在交替的日子里,将水与首选室配对。进行八次配对后,进行位置偏好测试,允许受试者进入两个室。一半的受试者在给予乙醇之前接受 PT150 治疗。另一半接受载体。在偏好测试期间记录每个室中的停留时间、配对期间的运动活动以及雌性鸟类的产蛋量。
乙醇处理导致 CPP,PT150 的预处理阻止了乙醇诱导的位置偏好的获得。乙醇或 PT150 均未改变运动活动。PT150 的预处理还增加了接受乙醇治疗的雌性鹌鹑的产蛋量。
这些发现表明,重复的乙醇与视觉线索配对可以产生 CPP。此外,PT150 的预处理可能是一种潜在的药理学治疗方法,可阻断乙醇的奖赏特性,并可增强接受乙醇治疗的雌性鹌鹑的产蛋量。