Guillem Karine, Peoples Laura L
Department of Integrative Neurophysiology, CNCR, VU University, Amsterdam, The Netherlands.
Behav Pharmacol. 2010 Mar;21(2):96-103. doi: 10.1097/FBP.0b013e328336e9c5.
This study tested the effects of the nicotine addiction treatment varenicline on cocaine self administration (SA) and reinstatement. In one SA experiment, rats were trained to self-administer cocaine (0.75 mg/kg/infusion). Thereafter, daily SA sessions continued as before except that every fourth session was preceded by a presession injection of varenicline (0.0, 0.3, 1.0 and 2.0 mg/kg, SC, 50-min presession). In three reinstatement experiments, animals were exposed sequentially to SA training, extinction training, and several reinstatement test sessions. In two of the reinstatement experiments, cocaine-seeking was reinstated by presentation of cocaine-predictive cues at the onset of the test session (cue reinstatement). In a third reinstatement experiment, cocaine-seeking was reinstated by a presession injection of cocaine (drug reinstatement). Each reinstatement session was preceded by an injection of either vehicle or varenicline (dose range of 0.1-2.0 mg/kg). The SA and reinstatement experiments showed that low-dose varenicline decreases reinstatement behavior, without significantly affecting cocaine SA. In contrast, high-dose varenicline increases reinstatement of cocaine-directed behavior and decreases cocaine SA. A control study showed that sucrose-directed behavior is unaltered by varenicline. On the basis of these findings, low-varenicline doses might decrease relapse in cocaine-addicted individuals, but high doses of varenicline might have the opposite effect.
本研究测试了尼古丁成瘾治疗药物伐尼克兰对可卡因自我给药（SA）及复吸的影响。在一项自我给药实验中，训练大鼠自我注射可卡因（0.75毫克/千克/次注射）。此后，每日的自我给药实验如前继续进行，但每四次实验前会在实验开始前50分钟皮下注射伐尼克兰（剂量分别为0.0、0.3、1.0和2.0毫克/千克）。在三项复吸实验中，动物依次接受自我给药训练、消退训练以及多次复吸测试实验。在两项复吸实验中，通过在测试实验开始时呈现可卡因预测线索来恢复对可卡因的寻觅行为（线索诱导复吸）。在第三项复吸实验中，通过在实验开始前注射可卡因来恢复对可卡因的寻觅行为（药物诱导复吸）。每次复吸实验前均会注射溶媒或伐尼克兰（剂量范围为0.1 - 2.0毫克/千克）。自我给药及复吸实验表明，低剂量伐尼克兰可降低复吸行为，而对可卡因自我给药无显著影响。相反，高剂量伐尼克兰会增加对可卡因相关行为的复吸，并减少可卡因自我给药。一项对照研究表明，伐尼克兰对蔗糖相关行为无影响。基于这些发现，低剂量伐尼克兰可能会降低可卡因成瘾个体的复吸率，但高剂量伐尼克兰可能会产生相反的效果。
