Li Fangqiong, Fang Qin, Liu Yu, Zhao Mei, Li Dapeng, Wang Jishi, Lu Lin
School of Pharmacology and the Affiliated Hospital of Guiyang Medical College, Guiyang, China.
Eur J Pharmacol. 2008 Jul 28;589(1-3):122-6. doi: 10.1016/j.ejphar.2008.04.051. Epub 2008 May 6.
Recent evidence suggests that cannabinoid CB(1) receptors may represent effective targets for therapeutic agents used to treat cocaine and heroin relapse. However, the role of cannabinoid CB(1) receptors in the potential treatment for other drugs of abuse is still largely unknown. The present study was conducted to determine whether cannabinoid CB(1) receptors play a similar role in relapse to ketamine abuse. To establish a ketamine reinstatement model in the conditioned place preference paradigm, rats were trained to develop place preference conditioned by ketamine, which was subsequently extinguished through daily exposure to the test chambers in the absence of ketamine. On the day following the last extinction session, four groups of rats were injected with ketamine (1, 5, 10 and 15 mg/kg, i.p.) to reinstate previously extinguished conditioned place preference. To investigate the effects of rimonabant, a cannabinoid CB(1) receptor antagonist, on reinstatement of ketamine-induced place preference, different doses of rimonabant (0.1, 0.5 and 3 mg/kg, i.p) were injected 30 min prior to the ketamine (5 and 15 mg/kg, i.p.) priming injection in a separate group of rats. To determine whether rimonabant itself produces conditioned place preference or conditioned place aversion, rats were trained for conditioned place preference or place aversion with rimonabant (0, 0.1, 0.5, 3.0 mg/kg, i.p.). While ketamine priming injections reinstated extinguished place preference, rimonabant administration significantly attenuated the reinstatement of ketamine-induced place preference in a dose-dependent manner. Importantly, rimonabant itself did not produce conditioned place preference or place aversion. Since the reinstatement effects of ketamine administration were inhibited by rimonabant, these findings suggest that a cannabinoid CB(1) receptor antagonist may be useful in preventing relapse to ketamine abuse.
最近的证据表明，大麻素CB(1)受体可能是用于治疗可卡因和海洛因复吸的治疗药物的有效靶点。然而，大麻素CB(1)受体在其他滥用药物潜在治疗中的作用仍 largely未知。本研究旨在确定大麻素CB(1)受体在氯胺酮滥用复吸中是否起类似作用。为在条件性位置偏爱范式中建立氯胺酮复吸模型，大鼠经训练形成对氯胺酮的位置偏爱条件，随后通过每天在无氯胺酮的情况下暴露于测试箱使其消退。在最后一次消退训练后的当天，四组大鼠注射氯胺酮（1、5、10和15mg/kg，腹腔注射）以恢复先前消退的条件性位置偏爱。为研究大麻素CB(1)受体拮抗剂利莫那班对氯胺酮诱导的位置偏爱恢复的影响，在另一组大鼠中，在氯胺酮（5和15mg/kg，腹腔注射）激发注射前30分钟注射不同剂量的利莫那班（0.1、0.5和3mg/kg，腹腔注射）。为确定利莫那班本身是否产生条件性位置偏爱或条件性位置厌恶，大鼠用利莫那班（0、0.1、0.5、3.0mg/kg，腹腔注射）进行条件性位置偏爱或位置厌恶训练。虽然氯胺酮激发注射恢复了消退的位置偏爱，但利莫那班给药以剂量依赖性方式显著减弱了氯胺酮诱导的位置偏爱恢复。重要的是，利莫那班本身未产生条件性位置偏爱或位置厌恶。由于利莫那班抑制了氯胺酮给药的恢复作用，这些发现表明大麻素CB(1)受体拮抗剂可能有助于预防氯胺酮滥用复吸。
