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.

阿片类药物成瘾在过去十年中大幅上升。迫切需要对抗鸦片上瘾的新疗法。当前的研究是为了确定使用短效合成阿片类药物瑞芬太尼在鸦片自我给药的大鼠模型中安非他酮和右美沙芬的急性个体和相互作用的作用。已经发现这两种药物都可以减少尼古丁的自我给药。安非他酮和右美沙芬及其组合具有不同的作用，这取决于大鼠显示瑞芬太尼的基线自我给药是较高还是较低。与媒介物对照条件相比，初始瑞米芬太尼自我给药较高的大鼠显示，安非他酮或右美沙芬治疗的瑞芬太尼自身给药显着降低。当联合使用较高剂量的安非他酮和右美沙芬时，这种自身瑞芬太尼给药的减少最为明显。相反，与媒介物对照条件相比，具有较低基线瑞芬太尼自我给药的大鼠显示出与药物治疗相反的作用，瑞芬太尼与安非他酮治疗的自我给药增加。右美沙芬在该组中无明显作用。这项研究表明，安非他酮和右美沙芬的组合以复杂的方式影响瑞芬太尼的自我给药，对低和高基线应答者有不同的作用。在瑞芬太尼自我给药基线较高的受试者中，安非他酮和右美沙芬治疗显着降低了自我给药，而在基线低瑞芬太尼自我给药的受试者中，安非他酮增加瑞芬太尼的自我给药，而右美沙芬没有明显的作用。这一发现表明，应在人体中对安非他酮-右美沙芬组合进行测试，重点在于治疗鸦片类药物大量使用的人。