Selective activation of AKAP150/TRPV1 in ventrolateral periaqueductal gray GABAergic neurons facilitates conditioned place aversion in male mice

被引:4
|
作者
Bai, Xiaohui [1 ,2 ]
Zhang, Kun [1 ]
Ou, Chaopeng [1 ]
Nie, Bilin [3 ]
Zhang, Jianxing [1 ]
Huang, Yongtian [1 ]
Zhang, Yingjun [1 ]
Huang, Jingxiu [1 ]
Ouyang, Handong [1 ]
Cao, Minghui [2 ]
Huang, Wan [1 ]
机构
[1] Sun Yat Sen Univ Canc Ctr, Collaborat Innovat Ctr Canc Med, Dept Anesthesiol, State Key Lab Oncol South China, Guangzhou, Peoples R China
[2] Sun Yat sen Univ, Sun Yat Sen Mem Hosp, Dept Anesthesiol, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangzhou, Peoples R China
[3] Guangdong Women & Children Hosp, Dept Anesthesiol, Guangzhou, Peoples R China
基金
中国国家自然科学基金;
关键词
RECEPTOR POTENTIAL V1; SYNAPTIC PLASTICITY; INFLAMMATORY PAIN; TRPV1; WITHDRAWAL; KINASE; EXPRESSION; RAT; PKA; ELECTROACUPUNCTURE;
D O I
10.1038/s42003-023-05106-4
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
AKAP150 modulates TRPV1 phosphorylation in GABAergic, but not glutamatergic, neurons of the ventrolateral periaqueductal gray to control conditioned place aversion in male mice Aversion refers to feelings of strong dislike or avoidance toward particular stimuli or situations. Aversion can be caused by pain stimuli and has a long-term negative impact on physical and mental health. Aversion can also be caused by drug abuse withdrawal, resulting in people with substance use disorder to relapse. However, the mechanisms underlying aversion remain unclear. The ventrolateral periaqueductal gray (vlPAG) is considered to play a key role in aversive behavior. Our study showed that inhibition of vlPAG GABAergic neurons significantly attenuated the conditioned place aversion (CPA) induced by hindpaw pain pinch or naloxone-precipitated morphine withdrawal. However, activating or inhibiting glutamatergic neurons, or activating GABAergic neurons cannot affect or alter CPA response. AKAP150 protein expression and phosphorylated TRPV1 (p-TRPV1) were significantly upregulated in these two CPA models. In AKAP150(flox/flox) mice and C57/B6J wild-type mice, cell-type-selective inhibition of AKAP150 in GABAergic neurons in the vlPAG attenuated aversion. However, downregulating AKAP150 in glutamatergic neurons did not attenuate aversion. Knockdown of AKAP150 in GABAergic neurons effectively reversed the p-TRPV1 upregulation in these two CPA models utilized in our study. Collectively, inhibition of the AKAP150/p-TRPV1 pathway in GABAergic neurons in the vlPAG may be considered a potential therapeutic target for the CPA response.
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页数:11
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