Martellotta M C, Cossu G, Fattore L, Gessa G L, Fratta W
Bernard B. Brodie Department of Neuroscience, University of Cagliari, Italy.
Neuroscience. 1998 Jul;85(2):327-30. doi: 10.1016/s0306-4522(98)00052-9.
Marijuana is one of the most widely used illicit recreational drugs. However, contrary to the majority of drugs abused by humans, there is a general opinion that rewarding effects are not manifested by animals. We studied a synthetic cannabinoid agonist WIN 55,212-2 using an intravenous self-administration model in drug-naive mice. The results of this study show that WIN 55,212-2 was intravenously self-administered by mice in a concentration-dependent manner according to a bell-shaped curve. Thus, self-administration of WIN 55,212-2 significantly increased, with respect to the vehicle self-administration control group, at concentrations of 0.5 and 0.1 mg/kg per injection. However, at WIN 55,212-2 concentration of 0.5 mg/kg per injection, self-administration significantly decreased. The results obtained show how WIN 55,212-2 is able to elicit both rewarding and aversive effects depending on the concentration used. Pretreatment of mice with the cannabinoid CB1 receptor antagonist SR 141716A (0.25 mg/kg, i.p.) completely prevented WIN 55,212-2 (0.1 mg/kg per injection) self-administration, indicating that WIN 55,212-2 rewarding effects are specifically mediated by cannabinoid CB1 receptors.
大麻是使用最为广泛的非法消遣性毒品之一。然而，与大多数人类滥用的毒品不同，人们普遍认为动物不会表现出奖赏效应。我们在未接触过药物的小鼠中使用静脉自我给药模型研究了一种合成大麻素激动剂WIN 55,212-2。本研究结果表明，WIN 55,212-2在小鼠中以浓度依赖性方式根据钟形曲线进行静脉自我给药。因此，相对于溶剂自我给药对照组，在每次注射浓度为0.5和0.1mg/kg时，WIN 55,212-2的自我给药显著增加。然而，在每次注射WIN 55,212-2浓度为0.5mg/kg时，自我给药显著减少。所获得的结果表明，WIN 55,212-2如何根据所使用的浓度引发奖赏和厌恶效应。用大麻素CB1受体拮抗剂SR 141716A（0.25mg/kg，腹腔注射）对小鼠进行预处理可完全阻止WIN 55,212-2（每次注射0.1mg/kg）的自我给药，表明WIN 55,212-2的奖赏效应是由大麻素CB1受体特异性介导的。
