大麻二酚调节甲基苯丙胺寻求行为消退和恢复的作用机制：以海马d2样多巴胺受体为靶点

IF 3.7 2区医学 Q1 PSYCHIATRY

Journal of psychiatric research Pub Date : 2025-06-11 DOI:10.1016/j.jpsychires.2025.06.011

Seyed Erfan Omidiani , Mahsa Mohammadi , Masoud Seddighfar , Ronak Azizbeigi , Abbas Haghparast

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引用次数: 0

摘要

甲基苯丙胺（冰毒）使用障碍是一个重大的公共卫生问题，缺乏有效和批准的药物治疗。大麻二酚是一种从大麻中提取的不会上瘾的化合物，作为一种潜在的治疗药物引起了人们的关注。然而，其对改善药物相关行为的作用机制尚不清楚。多种证据表明，CBD通过调节中皮质边缘多巴胺系统发挥其作用。海马CA1区的d2样受体在传递与药物相关线索加工相关的记忆和情绪信号中发挥重要作用。因此，本研究旨在探讨CA1 d2样受体在条件位置偏好（CPP）模型中介导CBD对灭绝和恢复过程中寻甲行为的影响中的作用。为此，大鼠在脑室内注射CBD （10 μg/5 μl）前，分别给予不同剂量的舒比利（0.25、1或4 μg/0.5 μl）作为d2样受体拮抗剂，持续10天。此外，另一组大鼠在恢复日单次注射CBD （50 μg/5 μl）之前先注射舒必利（0.25、1或4 μg/0.5 μl）。结果表明，舒必利（1和4 μg）显著减缓了CBD加速METH-CPP灭绝的作用(p <；0.01和p <；分别为0.05)。此外，恢复阶段的舒必利（1和4 μg）显著逆转了CBD对奖励寻求行为恢复的预防作用(p <；0.05和p <；分别为0.001)。总之，这些结果表明，CBD缩短消失期和抑制甲基安非他明恢复的能力部分是通过与海马CA1区d2样多巴胺受体的相互作用介导的。这些发现为更精确和有效地干预冰毒使用障碍提供了见解。

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Cannabidiol mechanism of action on modulating extinction and reinstatement of methamphetamine-seeking behavior: Targeting D2-like dopamine receptors in the hippocampus

Methamphetamine (METH) use disorder is a significant public health problem lacking effective and approved pharmacological treatments. Cannabidiol, a non-addictive compound derived from cannabis, has garnered attention as a potential therapeutic agent. However, the mechanisms underlying its effects on improving drug-related behaviors remain unclear. Multiple lines of evidence suggest that CBD exerts its effects by modulating the mesocorticolimbic dopamine system. D2-like receptors in the CA1 region of the hippocampus play a significant role in relaying memory and emotional signals related to the processing of drug-related cues. Therefore, this study aims to investigate the role of CA1 D2-like receptors in mediating the effects of CBD on METH-seeking behavior during extinction and reinstatement in the conditioned place preference (CPP) model. For this purpose, rats were administered various doses of Sulpiride (0.25,1, or 4 μg/0.5 μl) as a D2-like receptor antagonist before intracerebroventricular (ICV) injection of CBD (10 μg/5 μl) during a 10-day extinction period. Additionally, a separate group of rats received Sulpiride (0.25,1, or 4 μg/0.5 μl) before a single CBD injection (50 μg/5 μl) on the reinstatement day. The findings indicated that Sulpiride (1 and 4 μg) significantly attenuated CBD's acceleration of METH-CPP extinction (p < 0.01 and p < 0.05, respectively). Moreover, Sulpiride (1 and 4 μg) during the reinstatement phase notably reversed CBD's preventive effects on the reinstatement of reward-seeking behavior (p < 0.05 and p < 0.001, respectively). In summary, these results suggest that CBD's ability to shorten the extinction period and suppress METH reinstatement is partially mediated through interactions with D2-like dopamine receptors in the CA1 region of the hippocampus. These findings offering insight into more precise and effective interventions for METH use disorder.

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来源期刊

Journal of psychiatric research 医学-精神病学

CiteScore

7.30

自引率

2.10%

发文量

622

审稿时长

130 days

期刊介绍： Founded in 1961 to report on the latest work in psychiatry and cognate disciplines, the Journal of Psychiatric Research is dedicated to innovative and timely studies of four important areas of research: (1) clinical studies of all disciplines relating to psychiatric illness, as well as normal human behaviour, including biochemical, physiological, genetic, environmental, social, psychological and epidemiological factors; (2) basic studies pertaining to psychiatry in such fields as neuropsychopharmacology, neuroendocrinology, electrophysiology, genetics, experimental psychology and epidemiology; (3) the growing application of clinical laboratory techniques in psychiatry, including imagery and spectroscopy of the brain, molecular biology and computer sciences;