Sci Transl Med：丁丙诺啡和纳曲酮结合阻止可卡因成瘾

丁丙诺啡（Buprenorphine）是一种可激活μ和κ阿片受体的合成阿片类药物。它可以减少阿片类药物瘾君子可卡因的用量。然而，丁丙诺啡对μ阿片受体强有力的激动剂效应，使得它有可能造成非阿片依赖的可卡因滥用者对阿片的依赖。

研究者假设，结合丁丙诺啡和纳曲酮（naltrexone一种强力μ类阿片拮抗剂，同时具有较弱的δ和κ拮抗剂效果）可以阻止可卡因成瘾，同时避免产生阿片依赖。

研究者利用大鼠，对丁丙诺啡和不同剂量的纳曲酮对可卡因成瘾性的影响进行了评估，结果发现：单独应用丁丙诺啡可减少大鼠对可卡因的自我摄入。

同时摄入低剂量纳曲酮与丁丙诺啡的大鼠并没有表现出阿片戒断综合征，而在仅摄入丁丙诺啡的大鼠则出现了这样的表征。此外，纳曲酮在这个剂量并没有阻止κ类阿片受体激动剂诱导的镇痛作用。

研究结果表明，结合丁丙诺啡和纳曲酮在适当剂量下，减少可卡因成瘾同时产生最小可能的阿片依赖性。这可作为一个有用的治疗可卡因成瘾的方案。

doi:10.1016/j.cell.2011.10.017
PMC:
PMID:

A Combination of Buprenorphine and Naltrexone Blocks Compulsive Cocaine Intake in Rodents Without Producing Dependence

Sunmee Wee,Leandro F. Vendruscolo,Kaushik K. Misra,Joel E. Schlosburg andGeorge F. Koob*

Buprenorphine, a synthetic opioid that acts at both μ and κ opioid receptors, can decrease cocaine use in individuals with opioid addiction. However, the potent agonist action of buprenorphine at μ opioid receptors raises its potential for creating opioid dependence in non–opioid-dependent cocaine abusers. Here, we tested the hypothesis that a combination of buprenorphine and naltrexone (a potent μ opioid antagonist with weaker δ and κ antagonist properties) could block compulsive cocaine self-administration without producing opioid dependence. The effects of buprenorphine and various doses of naltrexone on cocaine self-administration were assessed in rats that self-administered cocaine under conditions of either short access (noncompulsive cocaine seeking) or extended access (compulsive cocaine seeking). Buprenorphine alone reproducibly decreased cocaine self-administration. Although this buprenorphine-alone effect was blocked in a dose-dependent manner by naltrexone in both the short-access and the extended-access groups, the combination of the lowest dose of naltrexone with buprenorphine blocked cocaine self-administration in the extended-access group but not in the short-access group. Rats given this low dose of naltrexone with buprenorphine did not exhibit the physical opioid withdrawal syndrome seen in rats treated with buprenorphine alone, and naltrexone at this dose did not block κ agonist–induced analgesia. The results suggest that the combination of buprenorphine and naltrexone at an appropriate dosage decreases compulsive cocaine self-administration with minimal liability to produce opioid dependence and may be useful as a treatment for cocaine addiction.