Abolghasemi Hedie, Shahani Pariya, Mozafari Roghayeh, Barikrow Nooshin, Yekta Batool Ghorbani, Haghparast Abbas
Department of Molecular and Cellular Sciences, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Physiol Behav. 2025 Jun 1;295:114894. doi: 10.1016/j.physbeh.2025.114894. Epub 2025 Mar 27.
Recent studies suggest that the nucleus accumbens (NAc) may influence the brain's response to pain signals, indicating a role beyond motivation and reward. The study delved into how the D1-like dopamine receptors (D1Rs) and μ-opioid receptors (MOR) interact in the NAc region in the context of formalin-induced pain. Rats received intra-accumbal various doses of morphine as an MOR agonist (5, 10, 25, and 50 mmol/0.5μl) and different doses of SKF38393 as a selective D1Rs agonist (1.5, 3, 6, and 12 mmol/0.5μl) in separate experimental groups, respectively. In the second stage, animals received different doses of SCH23390 as a selective D1Rs antagonist (1.5, 3, 6, and 12 mmol) before an effective dose of SKF38393 (6 mmol) and morphine (10 mmol). The rats were then given naloxone as an MOR antagonist (1.5, 5, and 15 mmol) before being given an effective dose of SKF38393 (6 mmol). In the formalin test, 50 µl formalin (2.5 %) was subcutaneously injected into the rat's hind paw to induce pain behavioral responses. The main findings indicated that the opioidergic and dopaminergic systems in the NAc region interact to create analgesic effects. The injection of morphine and SKF38393 into the NAc resulted in pain-relieving impacts. However, SCH23390 decreased the antinociceptive impacts of SKF38393 and morphine. Similarly, naloxone reduced the analgesic effects of SKF38393. The interactions between D1Rs and MOR can lead to synergistic effects. Therefore, using D1Rs agonists along with morphine can enhance the antinociceptive effect of morphine while reducing its side effects.
最近的研究表明，伏隔核（NAc）可能会影响大脑对疼痛信号的反应，这表明其作用超出了动机和奖赏范畴。该研究深入探讨了在福尔马林诱导的疼痛背景下，D1样多巴胺受体（D1Rs）和μ-阿片受体（MOR）在NAc区域是如何相互作用的。在不同的实验组中，大鼠分别接受了不同剂量的吗啡作为MOR激动剂（5、10、25和50 mmol/0.5μl）和不同剂量的SKF38393作为选择性D1Rs激动剂（1.5、3、6和12 mmol/0.5μl），通过脑内注射给药。在第二阶段，动物在接受有效剂量的SKF38393（6 mmol）和吗啡（10 mmol）之前，先接受了不同剂量的SCH23390作为选择性D1Rs拮抗剂（1.5、3、6和12 mmol）。然后，在给予大鼠有效剂量的SKF38393（6 mmol）之前，先给它们注射纳洛酮作为MOR拮抗剂（1.5、5和15 mmol）。在福尔马林试验中，将50 μl福尔马林（2.5%）皮下注射到大鼠的后爪，以诱导疼痛行为反应。主要研究结果表明，NAc区域的阿片能和多巴胺能系统相互作用，产生镇痛效果。向NAc注射吗啡和SKF38393会产生止痛作用。然而，SCH23390降低了SKF38393和吗啡的抗伤害感受作用。同样，纳洛酮降低了SKF38393的镇痛效果。D1Rs和MOR之间的相互作用可导致协同效应。因此，将D1Rs激动剂与吗啡联合使用可增强吗啡的抗伤害感受作用，同时减少其副作用。
