关键词: 5-HT2A receptor 5F-PB22 JWH-018 MDL100907 Mice Synthetic cannabinoids

Mesh : Humans Mice Male Animals Serotonin Cannabinoids / pharmacology Indoles / pharmacology Naphthalenes / toxicity Receptor, Cannabinoid, CB1

来  源:   DOI:10.1016/j.ejphar.2024.176486

Abstract:
Over the last years, Synthetic Cannabinoids (SCs) have been among the largest and most frequently seized groups of Novel Psychoactive Substances (NPS). These substances have been frequently detected in biological samples from patients involved in several intoxication and death cases. Their serious adverse effects have been related to their action as potent agonist of cannabinoid CB1 receptors. However, evidence concerning the potential interaction between SCs and serotoninergic mechanisms has emerged. Therefore, this study aims to evaluate the involvement of 5-HT2A receptors in the effects induced by acute systemic administration of 1-pentyl-3-(1-naphthoyl)indole (JWH-018; 1 mg/kg) and quinolin-8-yl 1-pentyfluoro-1H-indole-3-8-carboxylate (5F-PB22; 1 mg/kg). Sensorimotor (visual, acoustic, and tactile) responses, pain threshold (acute mechanical and thermal nociception), core temperature, breath rate and motor performance (stepping activity) have been assessed in CD-1 male mice. The present results pointed out that both substances deeply alter sensorimotor responses, nociceptive threshold, core temperature, breath rate and motor activity in mice. Noteworthy, pretreatment with the selective 5-HT2A receptors antagonist MDL100907 (0.1 mg/kg) at least partially prevented sensorimotor disruption, antinociception and hypothermic effects. Conversely, the respiratory and motor impairment was not prevented. Thus, it states the relevance of serotoninergic 5-HT2A mechanisms on pharmaco-toxicological effects induced by SCs.
摘要:
在过去的几年里,合成大麻素(SC)是新型精神活性物质(NPS)的最大和最频繁被缉获的群体之一。这些物质经常在涉及一些中毒和死亡病例的患者的生物样品中检测到。它们的严重不良反应与它们作为大麻素CB1受体的有效激动剂的作用有关。然而,关于SC和5-羟色胺能机制之间潜在相互作用的证据已经出现.因此,这项研究旨在评估5-HT2A受体在急性全身给药1-戊基-3-(1-萘甲酰基)吲哚(JWH-018;1mg/kg)和喹啉-8-1-戊基-1H-吲哚-3-8-羧酸酯(5F-PB22;1mg/kg)引起的效应中的参与。感觉运动(视觉,声学,和触觉)响应,痛阈值(急性机械和热伤害感受),核心温度,已经在CD-1雄性小鼠中评估了呼吸速率和运动性能(步进活动)。目前的结果指出,这两种物质都会深深地改变感觉运动反应,伤害性阈值,核心温度,小鼠的呼吸频率和运动活动。值得注意的是,用选择性5-HT2A受体拮抗剂MDL100907(0.1mg/kg)预处理至少部分防止感觉运动破坏,镇痛和低温效应。相反,呼吸和运动障碍未得到预防.因此,它阐明了5-羟色胺能5-HT2A机制与SC诱导的药物毒性作用的相关性。
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