The neuropharmacological properties of α-pyrrolidinobutiothiophenone, a new synthetic cathinone, in rodents; role of the dopaminergic system

IF 6.8 2区医学 Q1 PHARMACOLOGY & PHARMACY

British Journal of Pharmacology Pub Date : 2024-05-21 DOI:10.1111/bph.16422

Oc-Hee Kim, Kyung Oh Jeon, Gihyeon Kim, Choon-Gon Jang, Seong Shoon Yoon, Eun Young Jang

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引用次数: 0

Abstract

Background and Purpose

α-Pyrrolidinobutiothiophenone (α-PBT) is a chemical derivative of cathinone, a structural analogue of amphetamine. Until now, there have been a few previous neurochemical or neurobehavioural studies on the abuse potential of α-PBT.

Experimental Approach

We examined the abuse potential of α-PBT by measuring psychomotor, rewarding, and reinforcing properties and methamphetamine-like discriminative stimulus effects in rodents using locomotor activity, conditioned place preference, self-administration, and drug discrimination studies. To clarify the underlying neuropharmacological mechanisms, we measured dopamine levels and neuronal activation in the dorsal striatum. In addition, we investigated the role of the dopamine D₁ receptor or D₂ receptors in α-PBT-induced hyperlocomotor activity, conditioned place preference, and the methamphetamine-like discriminative stimulus effect of α-PBT in rodents.

Key Results

α-PBT promoted hyperlocomotor activity in mice. α-PBT induced drug-paired place preference in mice and supported self-administration in rats. In a drug discrimination experiment, α-PBT fully substituted for the discriminative stimulus effects of methamphetamine in rats. Furthermore, α-PBT increased dopamine levels and c-Fos expression in the dorsal striatum of mice, which was associated with these behaviours. Finally, pretreatment with the D₁ receptor antagonist SCH23390 or the D₂ receptors antagonist eticlopride significantly attenuated acute or repeated α-PBT-induced hyperlocomotor activity, place preference, and the methamphetamine-like discriminative stimulus effects in rodents.

Conclusions and Implications

These findings suggest that α-PBT has abuse potential at the highest dose tested via enhanced dopaminergic transmission in the dorsal striatum of rodents. The results provide scientific evidence for the legal restrictions of the recreational use of α-PBT.

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α-吡咯烷基丁硫酚酮（一种新型合成卡西酮）在啮齿动物体内的神经药理特性；多巴胺能系统的作用。

背景和目的：α-吡咯烷基丁硫茚酮（α-PBT）是卡西酮的化学衍生物，是苯丙胺的结构类似物。迄今为止，有关α-PBT滥用潜力的神经化学或神经行为学研究还为数不多：实验方法：我们通过运动活动、条件性位置偏好、自我给药和药物辨别研究，测量啮齿类动物的精神运动、奖赏和强化特性以及类似甲基苯丙胺的辨别刺激效应，来研究α-PBT的滥用潜力。为了阐明潜在的神经药理机制，我们测量了背侧纹状体中的多巴胺水平和神经元活化情况。此外，我们还研究了多巴胺D1受体或D2受体在α-PBT诱导的过度运动活动、条件性位置偏好和α-PBT对啮齿类动物的甲基苯丙胺样分辨刺激效应中的作用。在药物分辨实验中，α-PBT 完全替代了甲基苯丙胺对大鼠的分辨刺激作用。此外，α-PBT 还能增加小鼠背侧纹状体中的多巴胺水平和 c-Fos 表达，这与这些行为有关。最后，用D1受体拮抗剂SCH23390或D2受体拮抗剂依替氯必利（eticlopride）进行预处理，可显著减轻急性或重复α-PBT诱导的啮齿动物过度运动活动、位置偏好和类似甲基苯丙胺的辨别刺激效应：这些研究结果表明，α-PBT 通过增强啮齿动物背侧纹状体的多巴胺能传导，在最高剂量测试时具有滥用潜力。这些结果为从法律上限制α-PBT的娱乐性使用提供了科学证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

British Journal of Pharmacology 医学-药学

CiteScore

15.40

自引率

12.30%

发文量

270

审稿时长

2.0 months

期刊介绍： The British Journal of Pharmacology (BJP) is a biomedical science journal offering comprehensive international coverage of experimental and translational pharmacology. It publishes original research, authoritative reviews, mini reviews, systematic reviews, meta-analyses, databases, letters to the Editor, and commentaries. Review articles, databases, systematic reviews, and meta-analyses are typically commissioned, but unsolicited contributions are also considered, either as standalone papers or part of themed issues. In addition to basic science research, BJP features translational pharmacology research, including proof-of-concept and early mechanistic studies in humans. While it generally does not publish first-in-man phase I studies or phase IIb, III, or IV studies, exceptions may be made under certain circumstances, particularly if results are combined with preclinical studies.