The 5-HT7 receptors in the VLO contribute to the development of morphine-induced behavioral sensitization in rats

Jing-Si Yang; Fei-Fei Gao; Xi-Xi Yang; Feng Liang; Zhuo-Jin Yang; Jie Chen; Yu-Xiang Zhang; Chun-Xia Yan

doi:10.1016/j.neuint.2023.105566

The 5-HT₇ receptors in the VLO contribute to the development of morphine-induced behavioral sensitization in rats

Neurochem Int. 2023 Sep:168:105566. doi: 10.1016/j.neuint.2023.105566. Epub 2023 Jun 18.

Authors

Jing-Si Yang¹, Fei-Fei Gao¹, Xi-Xi Yang¹, Feng Liang², Zhuo-Jin Yang¹, Jie Chen¹, Yu-Xiang Zhang³, Chun-Xia Yan⁴

Affiliations

¹ College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China; The Key Laboratory of Forensic Medicine (Xi'an Jiaotong University) of the National Health Commission, Xi'an, Shaanxi, 710061, China; Academy of Bio-evidence Science, Science and Technology Innovation Port in Western China, Xi'an Jiaotong University, Xi-Xian New District, Shaanxi, 710115, China.
² College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China; The Key Laboratory of Forensic Medicine (Xi'an Jiaotong University) of the National Health Commission, Xi'an, Shaanxi, 710061, China.
³ College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China; The Key Laboratory of Forensic Medicine (Xi'an Jiaotong University) of the National Health Commission, Xi'an, Shaanxi, 710061, China; Academy of Bio-evidence Science, Science and Technology Innovation Port in Western China, Xi'an Jiaotong University, Xi-Xian New District, Shaanxi, 710115, China. Electronic address: yuxiangzhang@mail.xjtu.edu.cn.
⁴ College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China; The Key Laboratory of Forensic Medicine (Xi'an Jiaotong University) of the National Health Commission, Xi'an, Shaanxi, 710061, China; Academy of Bio-evidence Science, Science and Technology Innovation Port in Western China, Xi'an Jiaotong University, Xi-Xian New District, Shaanxi, 710115, China. Electronic address: yanchunxia@mail.xjtu.edu.cn.

PMID: 37339717
DOI: 10.1016/j.neuint.2023.105566

Abstract

The 5-hydroxytryptamine 7 receptor (5-HT₇R) is one of the most recently cloned serotonin receptors which have been implicated in many physiological and pathological processes including drug addiction. Behavioral sensitization is the progressive process during which re-exposure to drugs intensified the behavioral and neurochemical responses to drugs. Our previous study has demonstrated that the ventrolateral orbital cortex (VLO) is critical for morphine-induced reinforcing effect. The aim of the present study was to investigate the effect of 5-HT₇Rs in the VLO on morphine-induced behavioral sensitization and their underlying molecular mechanisms. Our results showed that a single injection of morphine, followed by a low challenge dose could induce behavioral sensitization. Microinjection of the selective 5-HT₇R agonist AS-19 into the VLO during the development phase significantly increased morphine-induced hyperactivity. Microinjection of the 5-HT₇R antagonist SB-269970 suppressed acute morphine-induced hyperactivity and the induction of behavioral sensitization, but had no effect on the expression of behavioral sensitization. In addition, the phosphorylation of AKT (Ser 473) was increased during the expression phase of morphine-induced behavioral sensitization. Suppression of the induction phase could also block the increase of p-AKT (Ser 473). In conclusion, we demonstrated that 5-HT₇Rs and p-AKT in the VLO at least partially contribute to morphine-induced behavioral sensitization.

Keywords: 5-HT(7)Rs; AKT; Behavioral sensitization; Morphine; Ventrolateral orbital cortex.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Morphine*
Prefrontal Cortex / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Rats
Rats, Sprague-Dawley
Serotonin* / metabolism

Substances

Morphine
Serotonin
Proto-Oncogene Proteins c-akt