大麻二酚类似物HU-502和HU-556诱导的行为效应。

IF 1.6 4区 心理学 Q3 BEHAVIORAL SCIENCES Behavioural Pharmacology Pub Date : 2023-06-01 DOI:10.1097/FBP.0000000000000727
Débora A E Colodete, Nicole R Silva, João Francisco C Pedrazzi, Manoela V Fogaça, Isadora Cortez, Elaine A Del-Bel, Aviva Breuer, Raphael Mechoulam, Felipe V Gomes, Francisco S Guimarães
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引用次数: 0

摘要

大麻二酚是一种植物大麻素,缺乏Δ9-tetrahydrocannabinol (THC)的拟精神特性,THC是主要的精神活性大麻成分。大麻二酚具有几种潜在的治疗特性,包括抗焦虑、抗抑郁和抗精神病;然而,大麻二酚的口服生物利用度较低,这限制了其临床应用。在这里,我们研究了两种大麻二酚类似物HU-502和HU-556在预测抗焦虑、抗抑郁和抗精神病作用的行为测试中是否比大麻二酚更有效。不同剂量(0.01-3 mg/kg;将HU-556和HU-502在雄性瑞士小鼠中进行腹腔注射测试,这些小鼠分别进行了升高+迷宫(EPM)、强迫游泳(FST)和安非他明诱导的脉冲前抑制(PPI)中断和过度运动。在这些试验中,大麻二酚在15-60 mg/kg的剂量范围内对小鼠有效。我们还研究了高剂量的HU-556(3和10 mg/kg)和HU-502 (10 mg/kg)是否产生大麻素四体(低运动、嗜睡、低体温和镇痛),这是由四氢大麻酚类化合物诱导的。HU-556(0.1和1 mg/kg)增加了EPM中张开臂进入的百分比(但没有增加时间),减少了FST中不活动的时间,并减弱了安非他明引起的PPI中断。HU-502(1和3 mg/kg)降低安非他明引起的过度运动和PPI损伤。高剂量的HU-556可引起嗜睡和低运动,而HU-502则没有。这些发现表明,与大麻二酚类似,HU-556可以诱导抗焦虑、抗抑郁和抗精神病样作用,而HU-502具有抗精神病特性。这些效应是在没有大麻素四体效应的剂量范围内发现的。
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Behavioral effects induced by the cannabidiol analogs HU-502 and HU-556.

Cannabidiol is a phytocannabinoid that lacks the psychotomimetic properties of Δ9-tetrahydrocannabinol (THC), the main psychoactive Cannabis sativa component. Cannabidiol has several potential therapeutic properties, including anxiolytic, antidepressant, and antipsychotic; however, cannabidiol has low oral bioavailability, which can limit its clinical use. Here, we investigated if two cannabidiol analogs, HU-502 and HU-556, would be more potent than cannabidiol in behavioral tests predictive of anxiolytic, antidepressant, and antipsychotic effects. Different doses (0.01-3 mg/kg; intraperitoneally) of HU-556 and HU-502 were tested in male Swiss mice submitted to the elevated plus maze (EPM), forced swimming test (FST), and amphetamine-induced-prepulse inhibition (PPI) disruption and hyperlocomotion. Cannabidiol is effective in these tests at a dose range of 15-60 mg/kg in mice. We also investigated if higher doses of HU-556 (3 and 10 mg/kg) and HU-502 (10 mg/kg) produced the cannabinoid tetrad (hypolocomotion, catalepsy, hypothermia, and analgesia), which is induced by THC-like compounds. HU-556 (0.1 and 1 mg/kg) increased the percentage of open arm entries (but not time) in the EPM, decreased immobility time in the FST, and attenuated amphetamine-induced PPI disruption. HU-502 (1 and 3 mg/kg) decreased amphetamine-induced hyperlocomotion and PPI impairment. HU-556, at high doses, caused catalepsy and hypolocomotion, while HU-502 did not. These findings suggest that similar to cannabidiol, HU-556 could induce anxiolytic, antidepressant, and antipsychotic-like effects and that HU-502 has antipsychotic properties. These effects were found at a dose range devoid of cannabinoid tetrad effects.

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来源期刊
Behavioural Pharmacology
Behavioural Pharmacology 医学-行为科学
CiteScore
3.40
自引率
0.00%
发文量
84
审稿时长
6-12 weeks
期刊介绍: Behavioural Pharmacology accepts original full and short research reports in diverse areas ranging from ethopharmacology to the pharmacology of schedule-controlled operant behaviour, provided that their primary focus is behavioural. Suitable topics include drug, chemical and hormonal effects on behaviour, the neurochemical mechanisms under-lying behaviour, and behavioural methods for the study of drug action. Both animal and human studies are welcome; however, studies reporting neurochemical data should have a predominantly behavioural focus, and human studies should not consist exclusively of clinical trials or case reports. Preference is given to studies that demonstrate and develop the potential of behavioural methods, and to papers reporting findings of direct relevance to clinical problems. Papers making a significant theoretical contribution are particularly welcome and, where possible and merited, space is made available for authors to explore fully the theoretical implications of their findings. Reviews of an area of the literature or at an appropriate stage in the development of an author’s own work are welcome. Commentaries in areas of current interest are also considered for publication, as are Reviews and Commentaries in areas outside behavioural pharmacology, but of importance and interest to behavioural pharmacologists. Behavioural Pharmacology publishes frequent Special Issues on current hot topics. The editors welcome correspondence about whether a paper in preparation might be suitable for inclusion in a Special Issue.
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