ElShebiney Shaimaa, Elgohary Rania, El-Shamarka Marwa, Mowaad Noha, Abulseoud Osama A
Department of Narcotics, Ergogenics, and Poisons, National Research Centre, Dokki, Cairo 12622, Egypt.
Department of Psychiatry and Psychology, Mayo Clinic, Phoenix, AZ 85001, USA.
Toxics. 2023 Apr 17;11(4):379. doi: 10.3390/toxics11040379.
We have examined the effects of four different polyphenols in attenuating heroin addiction using a conditioned place preference (CPP) paradigm. Adult male Sprague Dawley rats received heroin (alternating with saline) in escalating doses starting from 10 mg/kg, i.p. up to 80 mg/kg/d for 14 consecutive days. The rats were treated with distilled water (1 mL), quercetin (50 mg/kg/d), β-catechin (100 mg/kg/d), resveratrol (30 mg/kg/d), or magnolol (50 mg/kg/d) through oral gavage for 7 consecutive days, 30 min before heroin administration, starting on day 8. Heroin withdrawal manifestations were assessed 24 h post last heroin administration following the administration of naloxone (1 mg/kg i.p). Heroin CPP reinstatement was tested following a single dose of heroin (10 mg/kg i.p.) administration. Striatal interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) were quantified (ELISA) after naloxone-precipitated heroin withdrawal. Compared to the vehicle, the heroin-administered rats spent significantly more time in the heroin-paired chamber ( < 0.0001). Concomitant administration of resveratrol and quercetin prevented the acquisition of heroin CPP, while resveratrol, quercetin, and magnolol blocked heroin-triggered reinstatement. Magnolol, quercetin, and β-catechin blocked naloxone-precipitated heroin withdrawal and increased striatal IL-6 concentration ( < 0.01). Resveratrol administration was associated with significantly higher withdrawal scores compared to those of the control animals ( < 0.0001). The results of this study show that different polyphenols target specific behavioral domains of heroin addiction in a CPP model and modulate the increase in striatal inflammatory cytokines TNF-α and IL-6 observed during naloxone-precipitated heroin withdrawal. Further research is needed to study the clinical utility of polyphenols and to investigate the intriguing finding that resveratrol enhances, rather than attenuates naloxone-precipitated heroin withdrawal.
我们使用条件性位置偏爱（CPP）范式研究了四种不同多酚对减轻海洛因成瘾的作用。成年雄性Sprague Dawley大鼠腹腔注射海洛因（与生理盐水交替），剂量从10 mg/kg开始递增，直至80 mg/kg/d，连续14天。从第8天开始，在给予海洛因前30分钟，通过灌胃连续7天给大鼠服用蒸馏水（1 mL）、槲皮素（50 mg/kg/d）、β-儿茶素（100 mg/kg/d）、白藜芦醇（30 mg/kg/d）或厚朴酚（50 mg/kg/d）。在最后一次给予海洛因后24小时，注射纳洛酮（1 mg/kg腹腔注射）后评估海洛因戒断表现。在单次注射海洛因（10 mg/kg腹腔注射）后测试海洛因CPP复吸情况。在纳洛酮诱发的海洛因戒断后，通过酶联免疫吸附测定（ELISA）对纹状体白细胞介素6（IL-6）和肿瘤坏死因子α（TNF-α）进行定量分析。与赋形剂组相比，给予海洛因的大鼠在与海洛因配对的实验箱中停留的时间明显更长（<0.0001）。白藜芦醇和槲皮素联合给药可阻止海洛因CPP的形成，而白藜芦醇、槲皮素和厚朴酚可阻断海洛因诱发的复吸。厚朴酚、槲皮素和β-儿茶素可阻断纳洛酮诱发的海洛因戒断，并增加纹状体IL-6浓度（<0.01）。与对照动物相比,给予白藜芦醇的大鼠戒断评分显著更高（<0.0001）。本研究结果表明，在CPP模型中，不同的多酚靶向海洛因成瘾的特定行为领域，并调节在纳洛酮诱发的海洛因戒断期间观察到的纹状体炎性细胞因子TNF-α和IL-6的增加。需要进一步研究以探讨多酚的临床效用，并研究白藜芦醇增强而非减轻纳洛酮诱发的海洛因戒断这一有趣发现。
