5-羟色胺 2C 激动剂洛沙酮延迟静脉选择，并改变可卡因的主观和心血管效应：一项随机、对照的人体实验室研究。
The serotonin-2C agonist Lorcaserin delays intravenous choice and modifies the subjective and cardiovascular effects of cocaine: A randomized, controlled human laboratory study.
机构信息
Substance Abuse Research Laboratory, Kansas City Veterans Affairs Medical Center, 4801 Linwood Boulevard, Kansas City, MO 64128, United States of America.
Substance Abuse Research Laboratory, Kansas City Veterans Affairs Medical Center, 4801 Linwood Boulevard, Kansas City, MO 64128, United States of America; Department of Psychiatry, University of Kansas School of Medicine, Wichita, KS 67226, United States of America.
出版信息
Pharmacol Biochem Behav. 2019 May;180:52-59. doi: 10.1016/j.pbb.2019.02.010. Epub 2019 Feb 24.
BACKGROUND
Lorcaserin is a modestly selective agonist for 2C serotonin receptors (5-HTR) approved for weight-loss therapy. This class can attenuate cue-induced responding and drug taking in preclinical studies, but effects in humans have not been reported.
METHODS AND PARTICIPANTS
We evaluated effects of single 10 mg doses of lorcaserin on the subjective and reinforcing effects of cocaine, using a randomized, double-blind, within-subject, cross-over design. Male, non-treatment-seeking, regular cocaine users received either single doses of oral placebo (n = 9) or lorcaserin (n = 9), followed by low- or high- doses of intravenous cocaine (0.23 or 0.46 mg/kg-injection). They were then allowed to self-administer the lower dose of cocaine.
RESULTS
Cocaine was well tolerated after lorcaserin pretreatment. Oral lorcaserin did not modify the number of cocaine injections self-administered. However, it prolonged the time over which participants made intravenous choices relative to the duration of monetary (cash) decisions. Lorcaserin increased ratings of 'high' and 'stimulated' after low-dose cocaine or vehicle, but decreased craving for cocaine after intravenous vehicle. It also caused small but significant increases in heart rate following noncontingent injections of intravenous placebo or cocaine. When active cocaine was self-administered, lorcaserin decreased heart rate after selection of a monetary choice, but increased it following an intravenous choice.
CONCLUSIONS
Combined treatment with cocaine and lorcaserin was safe in a limited number of subjects, but did not diminish cocaine-motivated behavior or drug-induced 'high'. Some positive subjective effects of cocaine were enhanced by lorcaserin, and it delayed intravenous choices and decreased craving under some conditions. Effects on heart rate depended on the type of reinforcer being self-administered.
TRIAL REGISTRATION
clinicaltrials.gov Identifier, NCT02680288.
背景
氯卡色林是一种中等选择性 5-羟色胺 2C 受体激动剂（5-HTR），被批准用于减肥治疗。这一类药物可以在临床前研究中减弱线索诱导的反应和药物使用，但在人类中的效果尚未报道。
方法和参与者
我们使用随机、双盲、自身对照、交叉设计评估了单次 10mg 剂量的氯卡色林对可卡因的主观和强化作用的影响。男性、非治疗寻求者、经常使用可卡因的个体接受了口服安慰剂（n=9）或氯卡色林（n=9）的单次剂量，然后接受了低剂量或高剂量的静脉内可卡因（0.23 或 0.46mg/kg-注射）。然后，他们被允许自行注射较低剂量的可卡因。
结果
氯卡色林预处理后，可卡因的耐受性良好。口服氯卡色林并未改变参与者自行注射可卡因的次数。然而，它延长了参与者做出静脉内选择的时间，相对于货币（现金）决策的持续时间。氯卡色林增加了低剂量可卡因或载体后的“高”和“刺激”评分，但降低了静脉内载体后的可卡因渴求。它还导致在非条件性静脉内安慰剂或可卡因注射后，心率出现微小但显著的增加。当主动可卡因被自我给药时，氯卡色林在选择货币选择后降低了心率，但在静脉选择后增加了心率。
结论
在有限数量的个体中，联合使用可卡因和氯卡色林是安全的，但不能减少可卡因驱动的行为或药物诱导的“高”。氯卡色林增强了可卡因的一些正性主观效应，并在某些条件下延迟了静脉内选择和减少了渴求。心率的影响取决于自我给药的强化物类型。
试验注册
clinicaltrials.gov 标识符，NCT02680288。
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