Reinforcing Effects of Binary Mixtures of Common Bath Salt Constituents: Studies with 3,4-Methylenedioxypyrovalerone (MDPV), 3,4-Methylenedioxymethcathinone (Methylone), and Caffeine in Rats
Reinforcing Effects of Binary Mixtures of Common Bath Salt Constituents: Studies with 3,4-Methylenedioxypyrovalerone (MDPV), 3,4-Methylenedioxymethcathinone (Methylone), and Caffeine in Rats
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DOI：
10.1038/npp.2017.141
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发表时间：
2018-03-01
影响因子：
7.6
通讯作者：
Collins, Gregory T.
中科院分区：
文献类型：
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作者：
Gannon, Brenda M.;Galindo, Kayla I.;Collins, Gregory T.
浴盐的使用与高滥用率、毒性和死亡率有关。浴盐制剂通常含有多种药物的混合物，包括多种合成卡西酮（例如3,4-亚甲二氧基甲基戊酮（MDPV）或3,4-亚甲二氧基甲基卡西酮（甲基））或合成卡西酮和咖啡因；然而，关于浴盐成分之间的相互作用是否会导致浴盐制剂的滥用相关影响，人们知之甚少。本研究使用雄性Sprague-Dawley大鼠在递进比例计划下进行反应，以量化MDPV、甲基one和咖啡因单独或二元混合物（每种混合物n=12）的强化效果。以四种比例（10:1、3:1、1:1和1:3）对每种药物的平均ED50进行评估。剂量加性分析用于确定每种药物混合物中每个剂量对的预测加性效应。MDPV、甲基one和咖啡因保持剂量依赖性，其中MDPV是三种浴盐成分中最有效的，而咖啡因是最无效的。每一种浴盐混合物也保持了高水平的反应。虽然大多数浴盐混合物的相互作用倾向于加性，但也观察到超添加剂（3:1 MDPV：咖啡因，3:1和1:1甲基one：咖啡因）和亚添加剂（3:1,1:1和1:3 MDPV：甲基one）相互作用。总之，这些发现表明，浴盐制剂的组成对其强化效力和有效性都有影响，并表明成分药物之间的这种相互作用可能有助于人类浴盐使用者报告的使用模式和效果。
Bath salts use is associated with high rates of abuse, toxicity, and death. Bath salt preparations often contain mixtures of drugs including multiple synthetic cathinones (eg, 3,4-methylenedioxypyrovalerone (MDPV) or 3,4-methylenedioxymethcathinone (methylone)) or synthetic cathinones and caffeine; however, little is known about whether interactions among bath salt constituents contribute to the abuse-related effects of bath salts preparations. This study used male Sprague-Dawley rats responding under a progressive ratio schedule to quantify the reinforcing effectiveness of MDPV, methylone, and caffeine, administered alone and as binary mixtures (n=12 per mixture). Each mixture was evaluated at four ratios (10:1, 3::1, 1:1, and 1:3) relative to the mean ED50 for each drug alone. Dose-addition analyses were used to determine the predicted, additive effect for each dose pair within each drug mixture. MDPV, methylone, and caffeine maintained responding in a dose-dependent manner, with MDPV being the most potent and effective, and caffeine being the least potent and effective of the three bath salts constituents. High levels of responding were also maintained by each of the bath salts mixtures. Although the nature of the interactions tended toward additivity for most bath salts mixtures, supra-additive (3:1 MDPV:caffeine, and 3:1 and 1:1 methylone:caffeine) and sub-additive (3:1, 1:1, and 1:3 MDPV:methylone) interactions were also observed. Together, these findings demonstrate that the composition of bath salts preparations can have an impact on both their reinforcing potency and effectiveness, and suggest that such interactions among constituent drugs could contribute to the patterns of use and effects reported by human bath salts users.