Effects of the second-generation "bath salt" cathinone alpha-pyrrolidinopropiophenone (α-PPP) on behavior and monoamine neurochemistry in male mice.
Effects of the second-generation "bath salt" cathinone alpha-pyrrolidinopropiophenone (α-PPP) on behavior and monoamine neurochemistry in male mice.
复制标题
DOI：
10.1007/s00213-018-5044-z
复制
发表时间：
2019-03
影响因子：
3.4
通讯作者：
Murnane KS
中科院分区：
文献类型：
--
作者：
Ray A;Chitre NM;Daphney CM;Blough BE;Canal CE;Murnane KS
合成卡西酮（“浴盐”）是安非他明的β-酮类似物，但很少有研究检测其潜在的神经毒性作用。在本研究中，我们评估了暴露于第二代合成卡西酮α-吡咯烷二丙烯酮（α-PPP）的持续行为和神经化学效应。雄性Swiss-Webster小鼠以暴食样给药方案（QID, q2h）暴露于α-PPP （80mg/kg）。给药后4-5天评估行为，第二天评估神经化学。行为学研究采用高架正迷宫、y形迷宫和新物体识别测试。采用高压液相色谱法测定前额皮质和纹状体中多巴胺、血清素、去甲肾上腺素和多巴胺主要代谢物3,4-二羟基苯基乙酸（DOPAC）的区域水平。另外，采用遥测法评估α-PPP对运动活动和核心温度影响的时间过程。暴露于α-PPP显著损害了y形迷宫的表现，降低了新物体识别测试的整体探索活动，并导致单胺神经化学的区域特异性消耗。相比之下，在新物体识别测试中，它对高难度迷宫的表现和物体识别没有显著影响。α-PPP的运动刺激作用与可卡因（30mg/kg）相当，α-PPP （80mg/kg）不诱导高热。α-PPP暴露导致探索行为、空间工作记忆和单胺神经化学的持续变化。这项研究强调了α-PPP的潜在危险，包括潜在的神经毒性，并表明卡西酮持续不良作用的机制可能与安非他明不同。
Synthetic cathinones (“bath salts”) are β-ketone analogs of amphetamines, yet few studies have examined their potential neurotoxic effects. In the current study, we assessed the persistent behavioral and neurochemical effects of exposure to the second-generation synthetic cathinone α-pyrrolidinopropiophenone (α-PPP). Male, Swiss-Webster mice were exposed to α-PPP (80mg/kg) using a binge-like dosing regimen (QID, q2h). Behavior was assessed 4–5 days after the dosing regimen, and neurochemistry was assessed the following day. Behavior was studied using the elevated plus maze, Y-maze, and novel object recognition tests. Regional levels of dopamine, serotonin, norepinephrine, and the major dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were determined in the prefrontal cortex and striatum using high-pressure liquid chromatography. Additional experiments assessed the time courses of the effects of α-PPP on locomotor activity and core temperature using telemetry. Exposure to α-PPP significantly impaired performance in the Y-maze, decreased overall exploratory activity in the novel object recognition test, and resulted in regionally specific depletions in monoamine neurochemistry. In contrast, it had no significant effect on elevated plus maze performance or object discrimination in the novel object recognition test. The locomotor-stimulant effects of α-PPP were comparable to cocaine (30mg/kg), and α-PPP (80mg/kg) did not induce hyperthermia. α-PPP exposure results in persistent changes in exploratory behavior, spatial working memory, and monoamine neurochemistry. This research highlights potential dangers of α-PPP, including potential neurotoxicity, and suggests that the mechanisms underlying the persistent untoward effects of the cathinones may be distinct from those of the amphetamines.
登录
查看更多内容
影响因子：
4.7
作者：
Anneken JH;Angoa-Pérez M;Kuhn DM
通讯作者：
Kuhn DM
影响因子：
14.8
作者：
Leger, Marianne;Quiedeville, Anne;Freret, Thomas
通讯作者：
Freret, Thomas
影响因子：
5.1
作者：
MILLER, DB;OCALLAGHAN, JP
通讯作者：
OCALLAGHAN, JP
影响因子：
3.4
作者：
Murnane, Kevin Sean;Perrine, Shane Alan;Fantegrossi, William Edward
通讯作者：
Fantegrossi, William Edward
影响因子：
2.5
作者：
GONZALEZBURGOS, I;OLVERACORTES, E;FERIAVELASCO, A
通讯作者：
FERIAVELASCO, A