Psychopharmacology Laboratory, Center for Behavioral Neuroscience, American University, 4400 Massachusetts Ave, NW, Washington, DC, 20016, USA.
Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain.
Psychopharmacology (Berl). 2019 Mar;236(3):1067-1077. doi: 10.1007/s00213-018-5070-x. Epub 2018 Oct 17.
Work with α-pyrrolidinopentiophenone (α-PVP), a second-generation synthetic cathinone, has been generally limited to the racemate. Given that with other synthetic cathinones, there are behavioral and neurochemical differences between their enantiomers, differences may also be seen with α-PVP.
The present study assessed the relative contribution of each enantiomer to the aversive effects of racemic-α-PVP by comparing their ability to induce a conditioned taste avoidance.
Adult male Sprague-Dawley rats were exposed every other day for four exposures to a novel saccharin solution followed immediately by an injection of 0 (saline vehicle) or 1.5, 3, or 6 mg/kg of S-, R-, or racemic-α-PVP (IP). On alternating days, all subjects were given access to water to assess any unconditioned effects of α-PVP on general fluid consumption.
Rats injected with the racemate and S-isomer of α-PVP displayed avoidance of the drug-associated saccharin solution, although this avoidance was dose-dependent only for the subjects injected with the racemate. There was no evidence of taste avoidance in animals injected with the R-enantiomer at any dose tested. Animals injected with 3 mg/kg racemic-α-PVP did not differ in avoidance from those treated with 1.5 mg/kg of the S-enantiomer, but subjects treated with 6 mg/kg racemic-α-PVP displayed a significantly stronger avoidance than those treated with 3 mg/kg S-α-PVP.
The present work suggests that the aversive effects of racemic α-PVP are mediated primarily by its S-isomer. The fact that at the highest dose tested (6 mg/kg), the racemate induces an avoidance greater than the simple additive effects of the S- and R-isomers (at 3 mg/kg) suggests that while the R-isomer may not induce taste avoidance at this dose, it may interact synergistically with the S-isomer in mediating the effects of the racemic mixture. These results were discussed in terms of similar effects with other behavioral and physiological endpoints reported with a number of psychostimulants and suggest that the enantiomers of α-PVP are an important variable in characterizing its behavioral effects.
工作与 α- 吡咯烷酮戊基酮（α-PVP），一种第二代合成苯丙胺，一般限于外消旋体。鉴于其他合成苯丙胺，其对映体之间存在行为和神经化学差异，α-PVP 也可能存在差异。
本研究通过比较它们诱导条件味觉回避的能力，评估每个对映体对映体混合物致厌恶效应的相对贡献。
成年雄性 Sprague-Dawley 大鼠每隔一天暴露于一种新的蔗糖溶液中，然后立即注射 0（盐水载体）或 1.5、3 或 6mg/kg 的 S-、R-或外消旋-α-PVP（IP）。在交替的日子里，所有的动物都可以接触水，以评估 α-PVP 对一般液体消耗的任何非条件影响。
用外消旋体和 S-异构体注射α-PVP 的大鼠显示出对与药物相关的蔗糖溶液的回避，尽管这种回避仅对注射外消旋体的动物呈剂量依赖性。在任何测试剂量下，用 R-对映体注射的动物都没有表现出味觉回避。用 3mg/kg 外消旋-α-PVP 治疗的动物在回避方面与用 1.5mg/kg 的 S-对映体治疗的动物没有差异，但用 6mg/kg 外消旋-α-PVP 治疗的动物表现出比用 3mg/kg S-α-PVP 治疗的动物更强的回避。
本工作表明，外消旋 α-PVP 的厌恶效应主要由其 S-异构体介导。在测试的最高剂量（6mg/kg）下，外消旋体引起的回避大于 S-和 R-异构体（3mg/kg）的简单加和效应，这表明尽管 R-异构体在该剂量下可能不会引起味觉回避，但它可能与 S-异构体协同作用，介导混合物的效应。这些结果与其他几种精神兴奋剂报告的类似行为和生理终点的效应进行了讨论，并表明 α-PVP 的对映体是其行为效应特征的一个重要变量。
