Li Bing, Jiang Junyu, Zhou Li, Tao Xinrong, Sun Qixian, Liu Jiaxin, Liu Yang, Pang Gang
Center for Medical Research, School of Medicine, Anhui University of Science and Technology, Huainan, China.
College of Basic Medical Sciences, Anhui Medical University, Hefei, China.
Front Behav Neurosci. 2022 Feb 9;15:797217. doi: 10.3389/fnbeh.2021.797217. eCollection 2021.
Heroin dependency has become a global problem and has caused significant clinical and socioeconomic burdens along with devastating medical consequences. Chronic drug exposure alters the expression and functional activity of 5-hydroxytryptamine (serotonin) 2A receptors (5-HT2ARs) in the brain. Furthermore, pharmacological blockade of 5-HT2ARs reduces cue-induced cocaine craving behaviors. In this study, we explored the influence of 5-HT2ARs on heroin-withdrawal behaviors in mice. Black C57BL/6J mice were given gradually increasing (10-50 mg/kg over 4.5 days) doses of heroin to induce heroin dependency, after which naloxone was given to precipitate withdrawal symptoms. MDL100907, a selective and potent 5-HT2AR antagonist, attenuated naloxone-precipitated withdrawal symptoms in these mice. In addition, 5-HT2AR protein levels increased significantly in the medial prefrontal cortex (mPFC), while phosphorylation of extracellular signal-regulated kinase (p-ERK) decreased in the mPFC after heroin exposure. In conclusion, these results suggest that 5-HT2ARs might be involved in the development of opioid dependency and that pharmacological blocking of 5-HT2ARs might be a new therapeutic strategy for heroin dependency.
海洛因依赖已成为一个全球性问题，并带来了重大的临床和社会经济负担以及毁灭性的医学后果。长期药物暴露会改变大脑中5-羟色胺（血清素）2A受体（5-HT2ARs）的表达和功能活性。此外，对5-HT2ARs的药理学阻断可减少线索诱导的可卡因渴望行为。在本研究中，我们探讨了5-HT2ARs对小鼠海洛因戒断行为的影响。给黑色C57BL/6J小鼠逐渐增加（在4.5天内从10毫克/千克增加到50毫克/千克）海洛因剂量以诱导海洛因依赖，之后给予纳洛酮引发戒断症状。MDL100907，一种选择性且强效的5-HT2AR拮抗剂，减轻了这些小鼠中纳洛酮引发的戒断症状。此外，海洛因暴露后，内侧前额叶皮质（mPFC）中的5-HT2AR蛋白水平显著增加，而细胞外信号调节激酶（p-ERK）的磷酸化在mPFC中减少。总之，这些结果表明5-HT2ARs可能参与阿片类药物依赖的发展，并且对5-HT2ARs的药理学阻断可能是海洛因依赖的一种新治疗策略。
