Combined administration of buprenorphine and naltrexone produces antidepressant-like effects in mice
Combined administration of buprenorphine and naltrexone produces antidepressant-like effects in mice
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DOI：
10.1177/0269881115586937
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发表时间：
2015-07-01
影响因子：
4.1
通讯作者：
Bailey, Sarah J.
中科院分区：
文献类型：
--
作者：
Almatroudi, Abdulrahman;Husbands, Stephen M.;Bailey, Sarah J.
阿片类药物历来被用于治疗抑郁症。使用阿片类药物作为抗抑郁药的新兴趣集中在kappa阿片受体拮抗剂的开发上。丁丙诺啡作为部分阿片受体激动剂和受体拮抗剂。丁丙诺啡与阿片拮抗剂纳曲酮联用可降低-阿片受体的激活，增强-阿片受体的拮抗剂作用。我们已经确定，丁丙诺啡（1mg /kg）与纳曲酮（1mg /kg）的联合剂量在小鼠断尾试验中可作为短效拮抗剂。此外，这种剂量组合在条件位置偏好范式中既没有回报也没有厌恶，并且没有显著的运动效应。我们首次表明，在CD-1小鼠中，丁丙诺啡（1mg /kg）和纳曲酮（1mg /kg）在强迫游泳试验和新奇诱导的吞咽任务中的行为中产生了抗抑郁样反应。单用丁丙诺啡或联合纳曲酮治疗后，小鼠在高架加迷宫和光暗箱中的行为均无明显改变。我们认为丁丙诺啡与纳曲酮的结合代表了一种新的，并且可能是一种易于翻译的治疗抑郁症的方法。
Opiates have been used historically for the treatment of depression. Renewed interest in the use of opiates as antidepressants has focused on the development of kappa opioid receptor (-receptor) antagonists. Buprenorphine acts as a partial mu-opioid receptor agonist and a -receptor antagonist. By combining buprenorphine with the opioid antagonist naltrexone, the activation of mu-opioid receptors will be reduced and the -antagonist properties enhanced. We have established that a combination dose of buprenorphine (1 mg/kg) with naltrexone (1 mg/kg) functions as a short-acting -antagonist in the mouse tail withdrawal test. Furthermore, this dose combination is neither rewarding nor aversive in the conditioned place preference paradigm, and is without significant locomotor effects. We have shown for the first time that systemic co-administration of buprenorphine (1 mg/kg) with naltrexone (1 mg/kg) in CD-1 mice produced an antidepressant-like response in behaviours in both the forced swim test and novelty induced hypophagia task. Behaviours in the elevated plus maze and light dark box were not significantly altered by treatment with buprenorphine alone, or in combination with naltrexone. We propose that the combination of buprenorphine with naltrexone represents a novel, and potentially a readily translatable approach, to the treatment of depression.