Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.
Department of Medicine, Duke University School of Medicine, Durham, NC, USA; Duke Cancer Institute, Durham, NC, USA.
Pharmacol Biochem Behav. 2020 Jun;193:172919. doi: 10.1016/j.pbb.2020.172919. Epub 2020 Apr 1.
Opiate addiction has risen substantially during the past decade. New treatments to combat opiate addiction are sorely needed. The current study was conducted to determine the acute individual and interactive effects of bupropion and dextromethorphan in a rat model of opiate self-administration using the short-acting synthetic opioid remifentanil. Both of these drugs have been found to reduce self-administration of nicotine. Bupropion and dextromethorphan and their combination had differential effects depending on whether the rats showed higher or lower baseline remifentanil self-administration. The rats with higher initial remifentanil self-administration showed a significant decrease in remifentanil self-administration with bupropion or dextromethorphan treatment, compared to the vehicle control condition. This decrease in self-remifentanil administration was most pronounced when combination of the higher doses of bupropion and dextromethorphan were administered. In contrast, the rats with lower baseline remifentanil self-administration showed the opposite effect of drug treatment with an increase in remifentanil self-administration with bupropion treatment compared to the vehicle control condition. Dextromethorphan had no significant effect inthis group. This study shows that combination bupropion and dextromethorphan affects remifentanil self-administration in a complex fashion with differential effects on low and high baseline responders. In subjects with high baseline remifentanil self-administration, bupropion and dextromethorphan treatment significantly reduced self-administration, whereas in subjects with low baseline remifentanil self-administration, bupropion increased remifentanil self-administration and dextromethorphan had no discernible effect. This finding suggests that combination bupropion-dextromethorphan should be tested in humans, with a focus on treating people with high-level opiate use.
在过去的十年中，阿片类药物成瘾大幅上升。急需新的治疗方法来对抗阿片类药物成瘾。本研究旨在使用短效合成阿片类药物瑞芬太尼，确定丁丙诺啡和右美沙芬在阿片类药物自我给药大鼠模型中的急性个体和相互作用效应。这两种药物都被发现可以减少尼古丁的自我给药。丁丙诺啡和右美沙芬及其组合根据大鼠显示出更高或更低的基线瑞芬太尼自我给药而产生不同的效果。与载体对照条件相比，初始瑞芬太尼自我给药较高的大鼠用丁丙诺啡或右美沙芬治疗后，瑞芬太尼自我给药显著减少。当给予较高剂量的丁丙诺啡和右美沙芬组合时，这种自我给予瑞芬太尼的减少最为明显。相比之下，基线瑞芬太尼自我给药较低的大鼠在丁丙诺啡治疗后表现出相反的药物作用，与载体对照条件相比，瑞芬太尼自我给药增加。在该组中，右美沙芬没有显著作用。这项研究表明，丁丙诺啡和右美沙芬联合使用以复杂的方式影响瑞芬太尼自我给药，对低基线和高基线反应者有不同的影响。在基线瑞芬太尼自我给药较高的受试者中，丁丙诺啡和右美沙芬治疗显著减少了自我给药，而在基线瑞芬太尼自我给药较低的受试者中，丁丙诺啡增加了瑞芬太尼自我给药，而右美沙芬则没有明显作用。这一发现表明，丁丙诺啡-右美沙芬联合用药应在人类中进行测试，重点关注治疗高水平阿片类药物使用者。
