Laboratory of Neuropsychiatry, Psychiatric Center Copenhagen, Department O & Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark.
Pharmacol Biochem Behav. 2013 Apr;105:151-6. doi: 10.1016/j.pbb.2013.02.010. Epub 2013 Feb 27.
Several studies have suggested a role for neuropeptide Y (NPY) in addiction to drugs of abuse, including cocaine. Recently, our group showed a role for the NPY Y5 receptor in the modulation of acute reinforcing effects of cocaine using self-administration and hyperlocomotion paradigms. In the present study, we further explored potential anti-addiction-related effects of Y5 antagonism in another murine model of cocaine addiction-related behavior: conditioned place-preference (CPP). Using this model, it was tested whether blockade or deficiency of the NPY Y5 receptor could influence the induction, extinction or reinstatement of a conditioned cocaine response. We found that the Y5 antagonist L-152,804 causes faster extinction and reduced reinstatement of cocaine-induced CPP but did not reduce the ability of cocaine to induce CPP. Similarly, Y5-KO mice displayed faster extinction, and reinstatement of cocaine-induced CPP was absent. The development of CPP for cocaine was similar between Y5-KO and WT mice. Taken together, the present data show that Y5 antagonism attenuates relapse to cocaine addiction-related behavior. Prevention of relapse is considered to be of pivotal importance for the development of an effective treatment against cocaine addiction and therefore Y5 receptors could be a potential future therapeutic target in cocaine addiction.
几项研究表明，神经肽 Y（NPY）在药物成瘾中起作用，包括可卡因。最近，我们的研究小组表明，NPY Y5 受体在可卡因的急性强化作用的调节中起作用，使用自我给药和过度活跃的范式。在本研究中，我们使用另一种可卡因成瘾相关行为的小鼠模型，即条件性位置偏好（CPP），进一步探讨了 Y5 拮抗作用的潜在抗成瘾相关作用。使用这种模型，测试了 NPY Y5 受体的阻断或缺失是否会影响条件性可卡因反应的诱导、消退或恢复。我们发现，Y5 拮抗剂 L-152,804 导致可卡因诱导的 CPP 更快消退和减少恢复，但不减少可卡因诱导 CPP 的能力。同样，Y5-KO 小鼠表现出更快的消退，可卡因诱导的 CPP 恢复缺失。Y5-KO 和 WT 小鼠之间可卡因 CPP 的发展相似。总之，目前的数据表明 Y5 拮抗作用可减轻可卡因成瘾相关行为的复发。预防复发被认为是开发可卡因成瘾有效治疗方法的关键，因此 Y5 受体可能是可卡因成瘾的潜在未来治疗靶点。
