Blockade of 5-Hydroxytryptamine 2A Receptor Attenuates Precipitation of Naloxone-Induced Withdrawal Symptoms in Opioid-Exposed Mice

Frontiers in Behavioral Neuroscience

Junyu Jiang¹  Li Zhou¹  Jiaxin Liu¹  Bing Li¹  Xinrong Tao¹  Qixian Sun¹  Yang Liu¹  Gang Pang² 

[1] 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;

关键词: addiction;    serotonin;    5-HT2A R;    MDL100907;    heroin;    withdrawal;   

DOI  :  10.3389/fnbeh.2021.797217

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown