Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
Drug Alcohol Depend. 2020 Mar 1;208:107848. doi: 10.1016/j.drugalcdep.2020.107848. Epub 2020 Jan 17.
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-HT receptor agonists may attenuate the abuse-related effects of opioids. This study evaluated effectiveness of 7-day treatment with the clinically available 5-HT 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.
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).
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.
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.
当前的阿片类药物危机重新激发了评估阿片类药物使用障碍（OUD）非阿片类候选治疗方法的临床前研究。新出现的证据表明，5-HT 受体激动剂可能会减轻阿片类药物的滥用相关作用。本研究评估了临床可用的 5-HT 激动剂lorcaserin（Belviq®）在恒河猴中治疗 7 天对海洛因与食物选择的影响。将 lorcaserin 的作用与 7 天生理盐水替代和 7 天阿片类拮抗剂纳曲酮治疗的作用进行了比较。
成年雄性（1 只）和雌性（6 只）恒河猴接受训练，在每日 2 小时的时段内，通过同时进行食物输送（1 g 丸剂，固定比例 100 计划）和静脉内海洛因注射（0-0.032 mg/kg/注射，固定比例 10 计划）来做出反应。在 7 天生理盐水替代或 7 天连续纳曲酮（0.0032-0.032 mg/kg/h，IV）或 lorcaserin（0.032-0.32 mg/kg/h，IV）治疗之前和之后的每天测定海洛因选择剂量-效应函数。
在基线条件下，增加海洛因剂量可维持海洛因选择的剂量依赖性增加。生理盐水替代和 7 天纳曲酮治疗均显著减轻了海洛因的选择，并使食物选择呈反式增加。连续 lorcaserin（0.32 mg/kg/h）治疗显著增加了海洛因的选择。
与生理盐水替代和纳曲酮不同，lorcaserin 治疗不能减少海洛因与食物的选择。这些临床前结果不支持 lorcaserin 作为候选 OUD 治疗方法的治疗潜力和继续评估。
