Abbott Healthcare Products BV, C.J. van Houtenlaan 36, 1381 CP Weesp, The Netherlands.
Behav Brain Res. 2011 Mar 1;217(2):408-15. doi: 10.1016/j.bbr.2010.11.013. Epub 2010 Nov 11.
Cannabinoid CB(1) receptor (CB(1)R) signaling has been shown to play a role in the regulation of addictive behavior. In the present study, our aim was to investigate whether the CB(1)R antagonist SLV330 could reduce ethanol and nicotine self-administration and cue-induced reinstatement of ethanol and nicotine seeking behavior in Wistar rats. In operant chambers, rats were learned to emit a specific response (nose poke) in order to receive an ethanol solution or intravenous injections of nicotine. Discrete light and tone cues were presented during ethanol and nicotine delivery. These cues are particularly important for drug self-administration behavior and, through Pavlovian conditioning, acquire conditioned reinforcing and motivational properties and are therefore able to generate and maintain drug-seeking behavior. Subsequently, the CB(1)R antagonist SLV330 (doses ranging from 1 to 10mg/kg, given orally, p.o.) was administered to investigate the effects on drug self-administration. In addition, responding for ethanol and nicotine was extinguished. Then, the animals were tested for cue-induced reinstatement of ethanol and nicotine seeking and treated with vehicle or SLV330. Finally, the effects of SLV330 were studied on the number of anticipatory responses in the 5-choice serial reaction time task (5-CSRTT) in order to determine whether this compound could also increase impulse control in Wistar rats. The CB(1) antagonist SLV330 was effective in reducing ethanol self-administration at a lowest effective dose (LED) of 10mg/kg (p.o.) and reinstatement of ethanol seeking at a LED of 3mg/kg (p.o.). SLV330 was also effective in reducing nicotine self-administration and reinstatement of nicotine seeking, although at a LED of 10mg/kg (p.o.). Finally, SLV330 decreased time delay-dependent anticipatory responding (LED of 3.0mg/kg, p.o.), indicating an increased inhibitory control. These findings are in agreement with results reported with other CB(1) antagonists. The combined action of reducing the reinforcing and motivational properties of nicotine and alcohol and the improvement of impulse control supports the idea that the cannabinoid system is a promising target for anti-relapse medication.
大麻素 CB(1) 受体 (CB(1)R) 信号已被证明在调节成瘾行为中发挥作用。在本研究中，我们的目的是研究 CB(1)R 拮抗剂 SLV330 是否可以减少乙醇和尼古丁的自我给药以及乙醇和尼古丁寻求行为的线索诱导复燃。在操作性条件反射室中，大鼠学会发出特定的反应（鼻探查）以接收乙醇溶液或尼古丁的静脉注射。在乙醇和尼古丁给药期间呈现离散的光和声线索。这些线索对于药物自我给药行为非常重要，并且通过巴甫洛夫条件作用，获得条件强化和动机属性，因此能够产生和维持药物寻求行为。随后，给予 CB(1)R 拮抗剂 SLV330（剂量范围为 1 至 10mg/kg，口服给予），以研究其对药物自我给药的影响。此外，还消除了对乙醇和尼古丁的反应。然后，对动物进行乙醇和尼古丁寻求的线索诱导复燃测试，并给予载体或 SLV330 治疗。最后，研究了 SLV330 对 5 选择连续反应时间任务（5-CSRTT）中预期反应数量的影响，以确定该化合物是否还可以增加 Wistar 大鼠的冲动控制。CB(1) 拮抗剂 SLV330 在最低有效剂量 (LED) 为 10mg/kg（口服）时有效减少乙醇自我给药，在 LED 为 3mg/kg（口服）时有效减少乙醇寻求的复燃。SLV330 还有效减少尼古丁自我给药和尼古丁寻求的复燃，尽管在 LED 为 10mg/kg（口服）时。最后，SLV330 减少了时滞依赖性预期反应（LED 为 3.0mg/kg，口服），表明抑制控制增强。这些发现与其他 CB(1) 拮抗剂报告的结果一致。减少尼古丁和酒精的强化和动机特性以及改善冲动控制的联合作用支持大麻素系统是抗复发药物的有希望的靶标的观点。
