PDF(Pubmed)
Abstract：
BACKGROUND: Synthetic cathinones (SC) constitute the second most frequently abused class of new psychoactive substances. They serve as an alternative to classic psychostimulatory drugs of abuse, such as methamphetamine, cocaine, or 3,4-methylenedioxymethamphetamine (MDMA). Despite the worldwide prevalence of SC, little is known about their long-term impact on the central nervous system. Here, we examined the effects of repeated exposure of mice during infancy, to 3,4-methylenedioxypyrovalerone (MDPV), a SC potently enhancing dopaminergic neurotransmission, on learning and memory in young adult mice.
METHODS: All experiments were performed on C57BL/6J male and female mice. Animals were injected with MDPV (10 or 20 mg/kg) and BrdU (bromodeoxyuridine, 25 mg/kg) during postnatal days 11-20, which is a crucial period for the development of their hippocampus. At the age of 12 weeks, mice underwent an assessment of various types of memory using a battery of behavioral tests. Afterward, their brains were removed for detection of BrdU-positive cells in the dentate gyrus of the hippocampal formation with immunohistochemistry, and for measurement of the expression of synaptic proteins, such as synaptophysin and PSD95, in the hippocampus using Western blot.
RESULTS: Exposure to MDPV resulted in impairment of spatial working memory assessed with Y-maze spontaneous alternation test, and of object recognition memory. However, no deficits in hippocampus-dependent spatial learning and memory were found using the Morris water maze paradigm. Consistently, hippocampal neurogenesis and synaptogenesis were not interrupted. All observed MDPV effects were sex-independent.
CONCLUSIONS: MDPV administered repeatedly to mice during infancy causes learning and memory deficits that persist into adulthood but are not related to aberrant hippocampal development.
METHODS: All experiments were performed on C57BL/6J male and female mice. Animals were injected with MDPV (10 or 20 mg/kg) and BrdU (bromodeoxyuridine, 25 mg/kg) during postnatal days 11-20, which is a crucial period for the development of their hippocampus. At the age of 12 weeks, mice underwent an assessment of various types of memory using a battery of behavioral tests. Afterward, their brains were removed for detection of BrdU-positive cells in the dentate gyrus of the hippocampal formation with immunohistochemistry, and for measurement of the expression of synaptic proteins, such as synaptophysin and PSD95, in the hippocampus using Western blot.
RESULTS: Exposure to MDPV resulted in impairment of spatial working memory assessed with Y-maze spontaneous alternation test, and of object recognition memory. However, no deficits in hippocampus-dependent spatial learning and memory were found using the Morris water maze paradigm. Consistently, hippocampal neurogenesis and synaptogenesis were not interrupted. All observed MDPV effects were sex-independent.
CONCLUSIONS: MDPV administered repeatedly to mice during infancy causes learning and memory deficits that persist into adulthood but are not related to aberrant hippocampal development.
摘要：
背景：合成卡西酮（SC）是第二类最经常被滥用的新精神活性物质。它们可以替代经典的滥用精神刺激药物，比如甲基苯丙胺，可卡因,或3,4-亚甲二氧基甲基苯丙胺（MDMA）。尽管SC在世界范围内流行，人们对它们对中枢神经系统的长期影响知之甚少。这里,我们检查了在婴儿期反复暴露小鼠的影响，至3,4-亚甲二氧基戊酮（MDPV），SC能有效增强多巴胺能神经传递，对年轻成年小鼠学习和记忆的影响。
方法:所有实验在C57BL/6J雄性和雌性小鼠上进行。动物注射MDPV（10或20mg/kg）和BrdU（溴脱氧尿苷，25mg/kg）在出生后第11-20天，这是海马发育的关键时期。在12周龄时，使用一系列行为测试对小鼠进行了各种类型的记忆评估。之后,他们的大脑被切除，以通过免疫组织化学检测海马结构齿状回中的BrdU阳性细胞，为了测量突触蛋白的表达，如突触素和PSD95，在海马中使用蛋白质印迹。
结果：暴露于MDPV导致用Y-迷宫自发交替测验评估的空间工作记忆受损，和对象识别存储器。然而,使用Morris水迷宫范式，未发现海马依赖的空间学习和记忆缺陷。始终如一，海马神经发生和突触发生没有中断.所有观察到的MDPV效应均与性别无关。
结论：在婴儿期反复给予小鼠MDPV会导致学习和记忆缺陷，这种缺陷会持续到成年期，但与海马发育异常无关。
方法:所有实验在C57BL/6J雄性和雌性小鼠上进行。动物注射MDPV（10或20mg/kg）和BrdU（溴脱氧尿苷，25mg/kg）在出生后第11-20天，这是海马发育的关键时期。在12周龄时，使用一系列行为测试对小鼠进行了各种类型的记忆评估。之后,他们的大脑被切除，以通过免疫组织化学检测海马结构齿状回中的BrdU阳性细胞，为了测量突触蛋白的表达，如突触素和PSD95，在海马中使用蛋白质印迹。
结果：暴露于MDPV导致用Y-迷宫自发交替测验评估的空间工作记忆受损，和对象识别存储器。然而,使用Morris水迷宫范式，未发现海马依赖的空间学习和记忆缺陷。始终如一，海马神经发生和突触发生没有中断.所有观察到的MDPV效应均与性别无关。
结论：在婴儿期反复给予小鼠MDPV会导致学习和记忆缺陷，这种缺陷会持续到成年期，但与海马发育异常无关。
