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2-去氧皮帕罗尔对小鼠的奖赏效应。

Rewarding effects of 2-desoxypipradrol in mice.

机构信息

Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, 187 Osong Saengmyeong 2-ro, Heungdeok-gu, Chungju-shi, 28159, Republic of Korea.

Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, 187 Osong Saengmyeong 2-ro, Heungdeok-gu, Chungju-shi, 28159, Republic of Korea.

出版信息

Neurosci Lett. 2019 Jul 13;705:46-50. doi: 10.1016/j.neulet.2019.04.037. Epub 2019 Apr 18.

Abstract

Desoxypipradrol (2-DPMP), a new psychoactive substance (NPS), acts as a norepinephrine-dopamine reuptake inhibitor (NDRI). NDRIs can be addictive due to their action mechanisms similar to cocaine and methamphetamine. However, there is a lack of scientific information regarding the exact dependency of 2-DPMP. Thus, the purpose of this study was to evaluate rewarding and reinforcing effects of 2-DPMP in rodents. The effective dose range of 2-DPMP was determined by climbing behavior test. To evaluate rewarding effects of 2-DPMP, conditioned place preference (CPP) test was performed at selected doses in mice. Self-administration (SA) test was then undertaken at two doses that caused the highest effects in the CPP test. Dopamine level changes were analyzed using synaptosomes in order to investigate effects of 2-DPMP on the central nervous system (CNS). Significant responses were observed in the climbing behavior test at doses of 0.1, 0.5, and 1 mg/kg by intraperitoneal injection (i.p.). In the CPP test, mice i.p. administered 2-DPMP at 1 mg/kg showed a significant preference in drug-paired compartment. In the SA test, mice intravenously given 0.1 mg/kg/infusion showed significantly higher active lever responses. Further, dopamine was increased in a dose-dependent manner. Taken together, these results suggest that 2-DPMP may act on the CNS and induce rewarding and reinforcing effects, indicating its dependence liability.

摘要

地佐匹克隆(2-DPMP)是一种新型精神活性物质(NPS),作为去甲肾上腺素-多巴胺再摄取抑制剂(NDRI)。由于其作用机制类似于可卡因和甲基苯丙胺,NDRI 可能具有成瘾性。然而,关于 2-DPMP 的确切依赖性,目前缺乏科学信息。因此,本研究旨在评估 2-DPMP 在啮齿动物中的奖赏和强化作用。通过攀爬行为试验确定 2-DPMP 的有效剂量范围。为了评估 2-DPMP 的奖赏作用,在选定剂量下在小鼠中进行条件性位置偏好(CPP)试验。然后在 CPP 试验中引起最高效应的两个剂量下进行自我给药(SA)试验。使用突触体分析多巴胺水平变化,以研究 2-DPMP 对中枢神经系统(CNS)的影响。腹腔注射(i.p.)0.1、0.5 和 1mg/kg 时,在攀爬行为试验中观察到显著反应。在 CPP 试验中,腹腔注射 2-DPMP 1mg/kg 的小鼠在药物配对隔间中表现出显著的偏好。在 SA 试验中,静脉内给予 0.1mg/kg/输注的小鼠表现出明显更高的主动杠杆反应。此外,多巴胺呈剂量依赖性增加。总之,这些结果表明 2-DPMP 可能作用于中枢神经系统并诱导奖赏和强化作用,表明其依赖倾向。

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