Brutcher Robert E, Nader Michael A
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157-1083, USA.
Psychopharmacology (Berl). 2015 Jan;232(2):411-20. doi: 10.1007/s00213-014-3672-5. Epub 2014 Jul 17.
Clinical literature suggests a link between substance abuse and sleep disturbances. Quetiapine, an atypical antipsychotic, has shown efficacy in treating sleep disturbances, with clinical studies showing promise for quetiapine as a treatment for cocaine abuse.
The goal of this study was to examine the effects of quetiapine on cocaine self-administration and behavioral indices of sleep in monkeys.
Seven adult male rhesus monkeys, fitted with Actical® activity monitors, were trained to respond under a choice paradigm of food (1.0-g pellets) and cocaine (0.003-0.3 mg/kg per injection) presentation. First, monkeys received acute pretreatment (45 min) with quetiapine (25-75 mg, p.o.) prior to choice sessions; three cocaine doses were studied in combination with quetiapine. Next, the effect of chronic (14-16 days) quetiapine treatment (25-250 mg, p.o., BID) was examined in combination with the lowest preferred cocaine dose (≥80 % cocaine choice). Behavioral indices of sleep, based on activity measures obtained during lights-out, were recorded throughout the study.
Acute quetiapine decreased cocaine choice in four of the seven monkeys. Chronic quetiapine treatment resulted in initial decreases in cocaine choice, but tolerance developed to these effects. Acute doses of quetiapine did not improve sleep efficiency the following night nor did chronic quetiapine. The first night after discontinuing quetiapine treatment resulted in significant decreases in sleep efficiency and increases in nighttime activity.
These findings do not offer support for the use of quetiapine as a monotherapy for treatment of cocaine abuse nor as an adjunct therapy to treat sleep disturbances associated with stimulant abuse.
临床文献表明药物滥用与睡眠障碍之间存在联系。喹硫平作为一种非典型抗精神病药物,已显示出在治疗睡眠障碍方面的疗效,临床研究表明喹硫平有望用于治疗可卡因滥用。
本研究的目的是检验喹硫平对猴子可卡因自我给药及睡眠行为指标的影响。
七只成年雄性恒河猴,佩戴Actical®活动监测器,接受训练以在食物(1.0克颗粒)和可卡因(每次注射0.003 - 0.3毫克/千克)呈现的选择范式下做出反应。首先,猴子在选择实验前接受喹硫平(25 - 75毫克,口服)的急性预处理(45分钟);研究了三种可卡因剂量与喹硫平联合使用的情况。接下来,研究了慢性(14 - 16天)喹硫平治疗(25 - 250毫克,口服,每日两次)与最低偏好可卡因剂量(≥80%可卡因选择)联合使用的效果。在整个研究过程中,根据熄灯期间获得的活动测量记录睡眠行为指标。
急性给予喹硫平使七只猴子中的四只减少了对可卡因的选择。慢性喹硫平治疗导致最初可卡因选择减少,但对这些效果产生了耐受性。急性剂量的喹硫平在接下来的夜晚并未改善睡眠效率,慢性喹硫平也未改善。停止喹硫平治疗后的第一个晚上,睡眠效率显著降低,夜间活动增加。
这些发现不支持将喹硫平作为治疗可卡因滥用的单一疗法,也不支持作为治疗与兴奋剂滥用相关的睡眠障碍的辅助疗法。