Involvement of the opioid system in the anxiolytic-like effects induced by Δ9-tetrahydrocannabinol
Involvement of the opioid system in the anxiolytic-like effects induced by Δ9-tetrahydrocannabinol
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DOI：
10.1007/s00213-002-1144-9
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发表时间：
2002-08-01
影响因子：
3.4
通讯作者：
Maldonado, R
中科院分区：
文献类型：
--
作者：
Berrendero, F;Maldonado, R
基本原理：最近的研究表明，大麻素诱导的几种药理作用，包括抗伤害和奖励，涉及内源性阿片系统的参与。目的：本研究旨在探讨不同阿片受体参与Delta（9）-四氢大麻酚（THC）诱导的抗焦虑样反应的可能性。方法：给予低剂量THC（0.3 mg/kg）在光-暗箱中产生明显的抗焦虑样反应，如先前报道的。评价了CB1大麻素受体拮抗剂SR 141716 A（0.5 mg/kg）或μ-阿片受体拮抗剂β-funaltamine（5 mg/kg）、δ-阿片受体拮抗剂纳曲吲哚（2.5 mg/kg）和κ-阿片受体拮抗剂去甲-binaltorphimine（2.5 mg/kg）预处理对THC诱导的抗焦虑样反应的影响。结果如下：SR 141716 A完全阻断了THC诱导的抗焦虑样反应，表明这种作用是由CB 1大麻素受体介导的。β-阿片受体拮抗剂β-funalcidamine和δ-阿片受体拮抗剂纳曲吲哚，但不是κ-阿片受体拮抗剂norbinaltorphimine，废除THC抗焦虑样作用，表明参与的μ-和δ-阿片受体在这种行为反应。结论：这些结果表明，内源性阿片系统参与大麻素对焦虑样行为的调节，并为进一步阐明这两个神经元系统之间的相互作用提供了新的发现。
Rationale: Recent studies have shown that several pharmacological actions induced by cannabinoids, including antinociception and reward, involve the participation of the endogenous opioid system. Objectives: The present study was designed to examine the possible involvement of the different opioid receptors in the anxiolytic-like responses induced by Delta(9)-tetrahydrocannabinol (THC). Methods: The administration of a low dose of THC (0.3 mg/kg) produced clear anxiolytic-like responses in the light-dark box, as previously reported. The effects of the pretreatment with the CB1 cannabinoid receptor antagonist, SR 141716A (0.5 mg/kg), or the mu-opioid receptor antagonist, beta-funaltrexamine (5 mg/kg), the delta-opioid receptor antagonist, naltrindole (2.5 mg/kg) and the kappa-opioid receptor antagonist, nor-binaltorphimine (2.5 mg/kg) were evaluated on anxiolytic-like responses induced by THC. Results: SR 141716A completely blocked the anxiolytic-like response induced by THC, suggesting that this effect is mediated by CB1 cannabinoid receptors. The p-opioid receptor antagonist beta-funaltrexamine and the delta-opioid receptor antagonist naltrindole, but not the kappa-opioid receptor antagonist norbinaltorphimine, abolished THC anxiolytic-like effects, suggesting an involvement of mu- and delta-opioid receptors in this behavioural response. Conclusions: These results demonstrate that the endogenous opioid system is involved in the regulation of anxiety-like behaviour by cannabinoids and provide new findings to clarify further the interaction between these two neuronal systems.