Department Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.
Eur J Pharmacol. 2013 May 5;707(1-3):41-5. doi: 10.1016/j.ejphar.2013.03.021. Epub 2013 Mar 21.
We have previously shown that orphanin FQ (also known as nociceptin; OFQ/N) attenuates the motor stimulatory effect of cocaine and blocks locomotor sensitization induced by cocaine. Furthermore, we have shown that cocaine treatment altered the level of endogenous OFQ/N, raising the possibility that endogenous OFQ/N and its receptor (NOP) may be crucial in these actions of cocaine. Accordingly, in the present study, we sought to determine the role of NOP receptors in psychomotor stimulation and locomotor sensitization induced by cocaine or amphetamine. Mice lacking the NOP receptor and their wild-type littermates were habituated to motor activity chambers for 1h, injected with cocaine (0, 15 or 30 mg/kg) or amphetamine (0, 1 or 3mg/kg), and motor activity was recorded for 1h. For sensitization induced by these drugs, mice were treated with saline or the highest dose of each drug once daily for three consecutive days and tested on day 8. On this day, mice were habituated to the chambers for 1h, then received a challenge dose of cocaine (15 mg/kg) or amphetamine (1mg/kg), and motor activity was recorded for 1h. Cocaine and amphetamine each induced hyperlocomotion but the extent of this response was not different between NOP receptor null mice and their controls. Sensitization developed to the motor stimulatory action of each drug, but the magnitude of cocaine-induced sensitization was only higher in null mice compared to their controls. Together, the present results suggest that the endogenous OFQ/N/NOP receptor system may modulate the development of cocaine-induced locomotor sensitization.
我们之前已经表明孤啡肽（也称为 nociceptin；OFQ/N）可减弱可卡因的运动刺激作用，并阻断可卡因诱导的运动敏化。此外，我们还表明，可卡因处理改变了内源性 OFQ/N 的水平，这增加了内源性 OFQ/N 及其受体（NOP）在可卡因这些作用中可能很重要的可能性。因此，在本研究中，我们试图确定 NOP 受体在可卡因或安非他命引起的精神运动刺激和运动敏化中的作用。缺乏 NOP 受体的小鼠及其野生型同窝仔鼠适应运动活动室 1 小时，注射可卡因（0、15 或 30mg/kg）或安非他命（0、1 或 3mg/kg），并记录 1 小时的运动活动。对于这些药物引起的敏化，小鼠用盐水或每种药物的最高剂量每天处理一次，连续 3 天，并在第 8 天进行测试。在这一天，小鼠适应室 1 小时，然后接受挑战剂量的可卡因（15mg/kg）或安非他命（1mg/kg），并记录 1 小时的运动活动。可卡因和安非他命均可引起过度运动，但 NOP 受体缺失小鼠和对照小鼠之间的反应程度没有差异。每种药物的运动刺激作用都产生了敏化作用，但与对照相比，NOP 受体缺失小鼠中可卡因引起的敏化作用幅度更高。总之，目前的结果表明，内源性 OFQ/N/NOP 受体系统可能调节可卡因诱导的运动敏化的发展。
