Marquez Paul, Baliram Ramkumarie, Dabaja Ibrahim, Gajawada Nagaraju, Lutfy Kabirullah
Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.
Psychopharmacology (Berl). 2008 Apr;197(3):443-8. doi: 10.1007/s00213-007-1053-z. Epub 2008 Jan 6.
Opioid receptor antagonists have been shown to attenuate the rewarding and addictive effects of cocaine. Furthermore, cocaine has been shown to cause the release of beta-endorphin, an endogenous opioid peptide.
We assessed whether this neuropeptide would play a functional role in cocaine-induced motor stimulation and conditioned place preference (CPP).
Mice lacking beta-endorphin and their wild-type littermates were habituated to motor activity chambers for 1 h, then injected with cocaine (0, 15, 30, or 60 mg/kg, intraperitoneally) or morphine (0, 5, or 10 mg/kg, subcutaneously), and motor activity was recorded for 1 h. In the CPP paradigm, mice were tested for baseline place preference on day 1. On days 2 and 3, mice received an alternate-day saline/cocaine (15, 30, or 60 mg/kg) or saline/morphine (10 mg/kg) conditioning session and then tested for postconditioning place preference on day 4.
Cocaine-induced motor stimulation and CPP were both reduced in mice lacking beta-endorphin. On the other hand, motor stimulation and CPP induced by morphine were not altered in mutant mice.
The present results demonstrate that the endogenous opioid peptide beta-endorphin plays a modulatory role in the motor stimulatory and rewarding actions of acute cocaine.
阿片受体拮抗剂已被证明可减弱可卡因的奖赏和成瘾作用。此外，可卡因已被证明可导致内源性阿片肽β-内啡肽的释放。
我们评估了这种神经肽是否会在可卡因诱导的运动刺激和条件性位置偏爱（CPP）中发挥功能作用。
将缺乏β-内啡肽的小鼠及其野生型同窝小鼠在运动活动箱中适应1小时，然后腹腔注射可卡因（0、15、30或60mg/kg）或皮下注射吗啡（0、5或10mg/kg），并记录1小时的运动活动。在CPP范式中，在第1天测试小鼠的基线位置偏爱。在第2天和第3天，小鼠接受隔天的生理盐水/可卡因（15、30或60mg/kg）或生理盐水/吗啡（10mg/kg）条件训练，然后在第4天测试训练后的位置偏爱。
缺乏β-内啡肽的小鼠中，可卡因诱导的运动刺激和CPP均降低。另一方面，突变小鼠中吗啡诱导的运动刺激和CPP未改变。
目前的结果表明，内源性阿片肽β-内啡肽在急性可卡因的运动刺激和奖赏作用中起调节作用。
