Li Qian-Qian, Sun Cheng-Yu, Luo Yi-Xiao, Xue Yan-Xue, Meng Shi-Qiu, Xu Ling-Zhi, Chen Na, Deng Jia-Hui, Zhai Hai-Feng, Kosten Thomas R, Shi Jie, Lu Lin, Sun Hong-Qiang
Peking University Sixth Hospital/Institute of Mental Health (Dr Li, Ms C.-Y. Sun, Dr Luo, Ms Meng, Mr Xu, Ms Deng, Drs Lu, and H.-Q. Sun), and National Institute on Drug Dependence, Peking University, Beijing, China (Drs Dr Li, Ms C.-Y. Sun, Dr Luo, Dr Xue, Ms Meng, Mr Xu, Ms Chen, Ms Deng, Drs Zhai, Shi, and Lu); Institute for Food and Drug Safety Evaluation, National Institutes for Food and Drug Control, Beijing, China (Dr Li); Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, China (Drs Lu and H.-Q. Sun); Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas (Dr Kosten).
Peking University Sixth Hospital/Institute of Mental Health (Dr Li, Ms C.-Y. Sun, Dr Luo, Ms Meng, Mr Xu, Ms Deng, Drs Lu, and H.-Q. Sun), and National Institute on Drug Dependence, Peking University, Beijing, China (Drs Dr Li, Ms C.-Y. Sun, Dr Luo, Dr Xue, Ms Meng, Mr Xu, Ms Chen, Ms Deng, Drs Zhai, Shi, and Lu); Institute for Food and Drug Safety Evaluation, National Institutes for Food and Drug Control, Beijing, China (Dr Li); Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, China (Drs Lu and H.-Q. Sun); Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas (Dr Kosten)
Int J Neuropsychopharmacol. 2014 Dec 7;18(5):pyu093. doi: 10.1093/ijnp/pyu093.
Currently approved medications for opioid addiction have shown clinical efficacy, but undesired side effects, dependence induced by the medications themselves, and low treatment compliance necessitate the need for novel therapies.
A novel morphine-keyhole limpet hemocyanin conjugate vaccine was synthesized with 6-glutarylmorphine as the hapten and a lengthened linker of 6 carbon atoms. The titer and specificity of the triggered antibody were assessed by enzyme-linked immunosorbent assay. The effects of the vaccine on the morphine-induced elevation of dopamine levels in the nucleus accumbens were determined by high-performance liquid chromatography. The effects of the vaccine on morphine-induced locomotor sensitization and heroin-primed reinstatement of heroin self-administration were also assessed.
After subcutaneous administration in rats, the vaccine triggered a high antibody titer, with comparable specificity for morphine, 6-acetylmorphine, and heroin, but no interaction with dissimilar therapeutic opioid compounds, including buprenorphine, naloxone, and nalorphine, was observed. The vaccine significantly prevented the elevation of dopamine levels in the nucleus accumbens induced by a single morphine challenge. Moreover, the vaccine prevented the expression of morphine-induced locomotor sensitization and heroin-primed reinstatement of heroin seeking, suggesting its potential for preventing relapse.
These results demonstrate that active immunization with the present vaccine induces a robust morphine/heroin-specific antibody response in rats and attenuates the behavioral effects of morphine and heroin.
目前已获批用于治疗阿片类药物成瘾的药物已显示出临床疗效，但存在不良副作用、药物本身诱导的依赖性以及治疗依从性低等问题，因此需要新的治疗方法。
以6-戊二酰吗啡为半抗原，合成了一种新型的吗啡-钥孔戚血蓝蛋白缀合物疫苗，并使用了含6个碳原子的延长连接子。通过酶联免疫吸附测定法评估触发抗体的效价和特异性。通过高效液相色谱法测定疫苗对伏隔核中吗啡诱导的多巴胺水平升高的影响。还评估了疫苗对吗啡诱导的运动致敏和海洛因引发的海洛因自我给药复吸的影响。
在大鼠皮下注射后，该疫苗触发了高抗体效价，对吗啡、6-乙酰吗啡和海洛因具有相当的特异性，但未观察到与不同的治疗性阿片类化合物（包括丁丙诺啡、纳洛酮和烯丙吗啡）有相互作用。该疫苗显著预防了单次吗啡激发诱导的伏隔核中多巴胺水平的升高。此外，该疫苗预防了吗啡诱导的运动致敏的表达以及海洛因引发的海洛因觅药行为的复吸，表明其具有预防复发的潜力。
这些结果表明，用本疫苗进行主动免疫可在大鼠中诱导强烈的吗啡/海洛因特异性抗体反应，并减弱吗啡和海洛因的行为效应。
