School of Life Sciences, Arizona State University, Tempe, AZ, USA.
School of Biological Systems and Health Engineering, Arizona State University, Tempe, AZ, USA.
J Psychopharmacol. 2021 Oct;35(10):1216-1225. doi: 10.1177/02698811211019279. Epub 2021 May 28.
The 5-HT receptor (5-HTR) agonist, CP94253, enhances cocaine intake during maintenance of self-administration (SA) but attenuates intake after 21 days of forced abstinence in male rats.
We examined whether CP94253 attenuates cocaine intake in female rats after a period of abstinence, and if these attenuating effects persist or revert to enhancing cocaine intake during resumption (i.e. relapse) of daily cocaine SA.
Male and female rats trained to lever press on a fixed ratio 5 schedule of cocaine reinforcement underwent ⩾21 days of forced abstinence. They were then tested for the effects of CP94253 (5.6 mg/kg, SC) or vehicle on cocaine SA. During the test session, rats had 1-h access to the training dose of cocaine (0.75 mg/kg, IV) followed by 1-h access to a lower cocaine dose (0.075 mg/kg, IV). Rats then resumed cocaine SA for 15 days to mimic relapse and were retested as done previously. Subsequently, rats underwent abstinence again (21-60 days) and were tested for CP94253 effects on locomotion and cue reactivity (i.e. responding for light/tone cues previously paired with cocaine infusions).
Regardless of sex, CP94253 decreased cocaine intake after abstinence and during resumption of SA and decreased cue reactivity while having no effect on locomotion.
CP94253 decreases cocaine intake and cocaine seeking in both males and females even after resumption of cocaine SA. These findings suggest that the inhibitory effects of CP94253 observed after abstinence are long-lasting, and therefore, 5-HTR agonists may have clinical efficacy as anti-relapse medications for cocaine use disorders.
5-羟色胺受体（5-HTR）激动剂 CP94253 增强雄性大鼠维持自我给药（SA）期间的可卡因摄入量，但在 21 天强制戒断后减弱可卡因摄入量。
我们检测 CP94253 是否减弱雌性大鼠戒断后的可卡因摄入量，以及这些减弱作用是否在恢复（即复发）每日可卡因 SA 时持续或恢复增强可卡因摄入量。
接受可卡因强化训练的雄性和雌性大鼠进行了 ⩾21 天的强制戒断。然后，他们接受 CP94253（5.6mg/kg，SC）或载体对可卡因 SA 的影响测试。在测试期间，大鼠有 1 小时的时间接受训练剂量的可卡因（0.75mg/kg，IV），然后有 1 小时的时间接受较低剂量的可卡因（0.075mg/kg，IV）。然后，大鼠恢复可卡因 SA 15 天以模拟复发，并进行了与之前相同的测试。随后，大鼠再次进行戒断（21-60 天），并测试 CP94253 对运动和线索反应性（即对先前与可卡因输注配对的灯光/音调线索的反应）的影响。
无论性别如何，CP94253 均可减少戒断后和恢复 SA 期间的可卡因摄入量，并减少线索反应性，同时对运动没有影响。
CP94253 可减少男性和女性的可卡因摄入量和可卡因觅药行为，即使在恢复可卡因 SA 之后。这些发现表明，CP94253 在戒断后观察到的抑制作用是持久的，因此 5-HTR 激动剂可能具有作为可卡因使用障碍抗复发药物的临床疗效。
