Shahani Pariya, Abolghasemi Hedie, Abtin Shima, 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.
Pharmacol Biochem Behav. 2025 Jan;246:173911. doi: 10.1016/j.pbb.2024.173911. Epub 2024 Nov 23.
The opioidergic and dopaminergic systems play an essential role in processing pain information in the nucleus accumbens (NAc). The present work examined the hypothesis that interaction between opioidergic and D1-like dopamine receptors in the NAc area may influence acute pain-related behaviors. One hundred sixty adult male Wistar rats unilaterally received different doses of the drug solution or vehicle. First, separate groups of animals received different doses of morphine (5, 10, and 25 mmol/0.5 μL) and various doses of SKF38393 (1.5, 3, 6, and 12 mmol/0.5 μL) as opioid and D1-like receptor agonists in the NAc region, respectively. In the second set of experiments, animals got different amounts (1.5, 3, 6, and 12 mmol/0.5 μL) of SCH23390, a D1-like receptor antagonist, before an effective dose of morphine (10 mmol/0.5 μL). In the last experiment, the animals were given naloxone (1.5, 5, and 15 mmol/0.5 μL) before they were given an effective dose of SKF38393 (3 mmol/0.5 μL). The tail-flick test was then used to measure their acute pain threshold. The main findings showed that intra-NAc injection of morphine and SKF38393 alone causes antinociceptive responses. However, the intra-accumbal injection of SCH23390 significantly reduced the antinociceptive responses elicited by intra-NAc morphine. Additionally, intra-NAc naloxone significantly reduced the antinociceptive effects elicited by intra-NAc SKF38393. Interestingly, SCH23390 was more effective in reversing the analgesic effects of morphine (η2 = 0.61) than naloxone in reversing the analgesic effects of SKF38393 (η2 = 0.49). The findings suggest that the opioidergic and dopamine systems in the NAc collaborate to produce pain-relieving effects. This insight could potentially enhance the effectiveness of lower doses of opioids for pain management, ultimately reducing their usage in clinical settings in the future.
阿片能系统和多巴胺能系统在伏隔核（NAc）处理疼痛信息过程中发挥着重要作用。本研究检验了以下假设：NAc区域内阿片能受体与D1样多巴胺受体之间的相互作用可能会影响与急性疼痛相关的行为。160只成年雄性Wistar大鼠单侧接受不同剂量的药物溶液或赋形剂。首先，将动物分成不同组，分别在NAc区域注射不同剂量的吗啡（5、10和25 mmol/0.5 μL）和不同剂量的SKF38393（1.5、3、6和12 mmol/0.5 μL），分别作为阿片受体和D1样受体激动剂。在第二组实验中，动物在注射有效剂量的吗啡（10 mmol/0.5 μL）之前，先接受不同剂量（1.5、3、6和12 mmol/0.5 μL）的D1样受体拮抗剂SCH23390。在最后一组实验中，动物在注射有效剂量的SKF38393（3 mmol/0.5 μL）之前，先注射纳洛酮（1.5、5和15 mmol/0.5 μL）。然后使用甩尾试验测量它们的急性疼痛阈值。主要研究结果表明，单独向NAc内注射吗啡和SKF38393会引起抗伤害感受反应。然而，向伏隔核内注射SCH23390显著降低了NAc内注射吗啡所引发的抗伤害感受反应。此外，NAc内注射纳洛酮显著降低了NAc内注射SKF38393所引发的抗伤害感受作用。有趣的是，SCH23390在逆转吗啡镇痛作用方面（η2 = 0.61）比纳洛酮在逆转SKF38393镇痛作用方面（η2 = 0.49）更有效。研究结果表明，NAc内的阿片能系统和多巴胺系统协同作用产生镇痛效果。这一见解可能会提高低剂量阿片类药物用于疼痛管理的有效性，最终在未来减少其在临床环境中的使用。
