Discriminative stimulus effects of 3,4-methylenedioxypyrovalerone (MDPV) and structurally related synthetic cathinones.
Discriminative stimulus effects of 3,4-methylenedioxypyrovalerone (MDPV) and structurally related synthetic cathinones.
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DOI：
10.1097/fbp.0000000000000624
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发表时间：
2021-08-01
影响因子：
1.6
通讯作者：
Collins GT
中科院分区：
文献类型：
--
作者：
Seaman RW;Doyle MR;Sulima A;Rice KC;Collins GT
3，4-亚甲二氧基吡咯戊酮（MDPV）和其他结构相关的合成卡西酮是典型的非法精神兴奋剂（如可卡因和甲基苯丙胺）的流行替代品。这些药物通常被称为“浴盐”，并且作为单胺摄取的可卡因样抑制剂或多巴胺（DAT）、去甲肾上腺素（NET）和血清素（SERT）转运蛋白的安非他明样底物发挥作用。这些研究使用了接受过区分MDPV和生理盐水训练的雄性Sprague-Dawley大鼠，以评价结构相关的合成卡西酮、可卡因和其他直接作用的多巴胺和去甲肾上腺素能受体激动剂的取代特征，从而表征多巴胺、去甲肾上腺素和5-羟色胺对MDPV的区分刺激效应的相对贡献。正如预期的那样，卡西酮和可卡因中的每一种剂量依赖性地增加MDPV-适当的反应，等级顺序效力与其抑制DAT和NET的效力正相关，但与SERT无关，这种关系与维持自我给药的等级顺序一致。多巴胺D2/3受体首选激动剂喹吡罗可适度增加MDPV-适当反应，而多巴胺D1/5受体激动剂SKF 82958、非选择性多巴胺受体激动剂阿扑吗啡以及α-1和α-2肾上腺素能受体激动剂苯肾上腺素和可乐定分别可增加MDPV-适当反应，在小于完全抑制反应的剂量下，未能增加MDPV-适当反应。尽管这些研究不支持多巴胺能或肾上腺素能系统在介导/调节MDPV的辨别性刺激效应中的作用，但提供的会聚证据表明，MDPV的辨别性刺激效应主要由其抑制DAT的能力以及随后的多巴胺D2和/或D3受体的激活介导。
3,4-Methylenedioxypyrovalerone (MDPV), and other structurally-related synthetic cathinones, are popular alternatives to prototypical illicit psychostimulants, such as cocaine and methamphetamine. These drugs are often referred to as “bath salts”, and function either as cocaine-like inhibitors of monoamine uptake, or amphetamine-like substrates for dopamine (DAT), norepinephrine (NET), and serotonin (SERT) transporters. These studies used male Sprague-Dawley rats trained to discriminate MDPV from saline to evaluate the substitution profiles of structurally-related synthetic cathinones, cocaine, and other direct acting dopamine and noradrenergic receptor agonists in order to characterize the relative contributions of dopamine, norepinephrine, and serotonin to the discriminative stimulus effects of MDPV. As expected, each of the cathinones and cocaine dose-dependently increased MDPV-appropriate responding, with a rank order potency that was positively correlated with their potency to inhibit DAT and NET, but not SERT, a relationship that is consistent with the rank order to maintain self-administration. The dopamine D2/3 receptor-preferring agonist quinpirole produced a modest increase in MDPV-appropriate responding whilst the dopamine D1/5 receptor agonist, SKF 82958, non-selective dopamine receptor agonist, apomorphine, as well as the α–1, and α–2 adrenergic receptor agonists, phenylephrine and clonidine, respectively, failed to increase MDPV-appropriate responding at doses smaller than those that suppressed responding altogether. Although these studies do not support a role for serotonergic or adrenergic systems in mediating/modulating the discriminative stimulus effects of MDPV, convergent evidence is provided to suggest that the discriminative stimulus effects of MDPV are primarily mediated by its capacity to inhibit DAT, and the subsequent activation of dopamine D2 and/or D3 receptors.
影响因子：
3.4
作者：
Berquist MD 2nd;Thompson NA;Baker LE
通讯作者：
Baker LE
不同多巴胺受体亚型对可卡因在大鼠中的歧视性刺激作用的相对贡献。
影响因子：
3.4
作者：
Baladi, Michelle G.;Newman, Amy H.;France, Charles P.
通讯作者：
France, Charles P.