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首页> 外文期刊>The Journal of Pharmacology and Experimental Therapeutics: Official Publication of the American Society for Pharmacology and Experimental Therapeutics >Combination of Levo-Tetrahydropalmatine and Low Dose Naltrexone: A Promising Treatment for Prevention of Cocaine Relapse
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Combination of Levo-Tetrahydropalmatine and Low Dose Naltrexone: A Promising Treatment for Prevention of Cocaine Relapse

机译：左旋四氢巴马汀和小剂量纳曲酮的组合：预防可卡因复发的有希望的治疗方法。

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Relapse to drug use is often cited as the major obstacle in overcoming a drug addiction. Whereas relapse can occur for a myriad of reasons, it is well established that complex neuroadaptations that occur over the course of addiction are major factors. Cocaine, as a potent dopamine transporter blocker, specifically induces alterations in the dopaminergic as well as other monoaminergic neurotransmissions, which lead to cocaine abuse and dependence. Evidence also suggests that adaptations in the endogenous opioids play important roles in pathophysiology of cocaine addiction. Following this evidence, we investigated a combination medication, levo-tetrahydropalmatine (L-THP) and low dose naltrexone (LDN), targeting primarily dopaminergic and endogenous opioid systems as a cocaine-relapse-prevention treatment. In the present study Wistar rats were used to assess the effects of L-THP and LDN on cocaine self-administration, drug-seeking behavior during cocaine reinstatement, spontaneous locomotion, and effects on the endogenous opioid system. We determined that the combination of L-THP and LDN reduces drug-seeking behavior during reinstatement more potently than L-THP alone. Additionally, the combination of L-THP and LDN attenuates the sedative locomotor effect induced by L-THP. Furthermore, we revealed that treatment with the combination of L-THP and LDN has an upregulatory effect on both plasma beta-endorphin and hypothalamic POMC that was not observed in L-THP-treated groups. These results suggest that the combination of L-THP and LDN has great potential as an effective and well-tolerated medication for cocaine relapse prevention.
机译：经常提到吸毒复发是克服药物成瘾的主要障碍。尽管复发的原因可能多种多样，但众所周知，成瘾过程中发生的复杂神经适应是主要因素。可卡因作为一种有效的多巴胺转运蛋白阻滞剂，可特异性地引起多巴胺能以及其他单胺能神经传递的改变，从而导致可卡因滥用和依赖性。证据还表明，内源性阿片类药物的适应性在可卡因成瘾的病理生理中起着重要作用。根据这一证据，我们研究了联合用药，左旋四氢巴马汀（L-THP）和低剂量纳曲酮（LDN），主要针对多巴胺能和内源性阿片类药物系统，以预防可卡因复发。在本研究中，Wistar大鼠用于评估L-THP和LDN对可卡因自我给药，可卡因恢复期间的寻药行为，自发运动以及对内源性阿片样物质系统的影响。我们确定L-THP和LDN的组合比单独使用L-THP更有效地减少了恢复过程中的药物寻找行为。另外，L-THP和LDN的组合减弱了由L-THP诱导的镇静运动作用。此外，我们发现L-THP和LDN的组合治疗对血浆β-内啡肽和下丘脑POMC都有上调作用，这在L-THP治疗组中未观察到。这些结果表明，L-THP和LDN的组合作为预防可卡因复发的有效且耐受性良好的药物具有巨大潜力。

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