CB2 激动剂能减轻可卡因诱导的小鼠位置偏好恢复并调节炎症反应。

IF 1.6 4区 心理学 Q3 BEHAVIORAL SCIENCES Behavioural Pharmacology Pub Date : 2023-12-13 DOI:10.1097/fbp.0000000000000759
Oualid Abboussi, Zmarak Ahmad Khan, Hind Ibork, Simo S Zulu, William Daniels, Khalid Taghzouti, Tim G Hales
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引用次数: 0

摘要

众所周知,长期接触可卡因会对大脑产生深远影响,导致炎症信号通路失调、小胶质细胞活化以及认知和动机行为障碍。内源性大麻素系统已成为可卡因有害影响的潜在媒介。在本研究中,我们试图研究大麻素 CB2 受体激动剂 JWH-133 在减轻可卡因诱导的炎症和相关动机行为改变的体内模型中的治疗潜力。我们的研究发现了令人信服的证据,即选择性 CB2 受体激动剂 JWH-133 能显著抑制可卡因诱导的条件性位置偏好的恢复。这种效应伴随着神经生物学景观的显著变化。具体来说,研究发现服用 JWH-133 会上调伏隔核(Nac)中 Δ-FOSB 的表达,提高腹侧被盖区和前额叶皮层(PFC)中 CX3CL1 的水平,同时降低可卡因处理动物 PFC 和 NAc 中 IL-1β 的表达。这些发现凸显了CB2大麻素受体激活在改变可卡因诱导的寻求奖赏行为中的调节作用。此外,它们还揭示了内源性大麻素系统与可卡因诱导的神经生物学变化之间错综复杂的相互作用,为针对可卡因成瘾和相关行为缺陷的CB2受体的潜在治疗干预铺平了道路。
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CB2 agonist mitigates cocaine-induced reinstatement of place preference and modulates the inflammatory response in mice.
Chronic exposure to cocaine is known to have profound effects on the brain, leading to the dysregulation of inflammatory signalling pathways, the activation of microglia, and the manifestation of cognitive and motivational behavioural impairments. The endocannabinoid system has emerged as a potential mediator of cocaine's deleterious effects. In this study, we sought to investigate the therapeutic potential of the cannabinoid CB2 receptor agonist, JWH-133, in mitigating cocaine-induced inflammation and associated motivational behavioural alterations in an in vivo model. Our research uncovered compelling evidence that JWH-133, a selective CB2 receptor agonist, exerts a significant dampening effect on the reinstatement of cocaine-induced conditioned place preference. This effect was accompanied by notable changes in the neurobiological landscape. Specifically, JWH-133 administration was found to upregulate Δ-FOSB expression in the nucleus accumbens (Nac), elevate CX3CL1 levels in both the ventral tegmental area and prefrontal cortex (PFC), and concurrently reduce IL-1β expression in the PFC and NAc among cocaine-treated animals. These findings highlight the modulatory role of CB2 cannabinoid receptor activation in altering the reward-seeking behaviour induced by cocaine. Moreover, they shed light on the intricate interplay between the endocannabinoid system and cocaine-induced neurobiological changes, paving the way for potential therapeutic interventions targeting CB2 receptors in the context of cocaine addiction and associated behavioural deficits.
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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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