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Lorcaserin maintenance fails to attenuate heroin vs. food choice in rhesus monkeys.
Drug and Alcohol Dependence ( IF 3.9 ) Pub Date : 2020-01-17 , DOI: 10.1016/j.drugalcdep.2020.107848
E Andrew Townsend 1 , S Stevens Negus 1 , Justin L Poklis 1 , Matthew L Banks 1
Affiliation  

BACKGROUND The current opioid crisis has reinvigorated preclinical research in the evaluation of non-opioid candidate treatments for opioid use disorder (OUD). Emerging evidence suggests 5-HT2C receptor agonists may attenuate the abuse-related effects of opioids. This study evaluated effectiveness of 7-day treatment with the clinically available 5-HT2C agonist lorcaserin (Belviq®) on heroin-vs.-food choice in rhesus monkeys. Lorcaserin effects were compared to effects produced by 7-day saline substitution and by 7-day treatment with the opioid antagonist naltrexone. METHODS Adult male (1) and female (6) rhesus monkeys were trained to respond under a concurrent schedule of food delivery (1 g pellets, fixed-ratio 100 schedule) and intravenous heroin injections (0-0.032 mg/kg/injection, fixed-ratio 10 schedule) during daily 2 h sessions. Heroin choice dose-effect functions were determined daily before and following 7-day saline substitution or 7-day continuous treatment with naltrexone (0.0032-0.032 mg/kg/h, IV) or lorcaserin (0.032-0.32 mg/kg/h, IV). RESULTS Under baseline conditions, increasing heroin doses maintained a dose-dependent increase in heroin choice. Both saline substitution and 7-day naltrexone treatment significantly attenuated heroin choice and produced a reciprocal increase in food choice. Continuous lorcaserin (0.32 mg/kg/h) treatment significantly increased heroin choice. CONCLUSIONS In contrast to saline substitution and naltrexone, lorcaserin treatment was ineffective to reduce heroin-vs.-food choice. These preclinical results do not support the therapeutic potential and continued evaluation of lorcaserin as a candidate OUD treatment.

中文翻译:


维持绿卡色林未能减弱恒河猴的海洛因与食物选择的影响。



背景当前的阿片类药物危机重振了评估阿片类药物使用障碍(OUD)的非阿片类候选疗法的临床前研究。新证据表明 5-HT2C 受体激动剂可能会减弱阿片类药物滥用相关的影响。本研究评估了临床可用的 5-HT2C 激动剂氯卡色林 (Belviq®) 7 天治疗对恒河猴海洛因与食物选择的有效性。将氯卡色林的效果与 7 天盐水替代和阿片拮抗剂纳曲酮 7 天治疗产生的效果进行比较。方法 训练成年雄性(1 只)和雌性(6 只)恒河猴在同时进行的食物输送(1 g 丸剂,固定比例 100 方案)和静脉注射海洛因注射(0-0.032 mg/kg/注射,固定)下做出反应。 - 每日 2 小时训练期间的比率 10 计划)。在 7 天盐水替代或 7 天连续治疗纳曲酮(0.0032-0.032 mg/kg/h,IV)或氯卡色林(0.032-0.32 mg/kg/h,IV)之前和之后每天确定海洛因选择剂量效应函数)。结果 在基线条件下,海洛因剂量的增加使海洛因选择呈剂量依赖性增加。盐水替代和 7 天纳曲酮治疗均显着减少了海洛因的选择,并相应增加了食物的选择。连续氯卡色林(0.32 mg/kg/h)治疗显着增加了海洛因的选择。结论 与盐水替代和纳曲酮相比,氯卡色林治疗无法有效减少海洛因与食物的选择。这些临床前结果不支持氯卡色林作为候选 OUD 治疗的治疗潜力和持续评估。
更新日期:2020-01-17
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