Depressive-like state sensitizes 5-HT1A and 5-HT1B auto-receptors in the dorsal raphe nucleus sub-system.

Xiang Li, Xianan Sun, Jing Sun, Yi Zu, Shulei Zhao, Xiao Sun, Lu Li, Xinjing Zhang, Wei Wang, Yuezhu Liang, Wenyao Wang, Xuankai Liang, Chi Sun, Xue Guan, Man Tang

Behavioural brain research 2020 Jul 01

filter terms:

Dorsal raphe (DR) and median raphe (MR) 5-HT neurons are two distinct sub-systems known to be regulated by 5-HT1A and 5-HT1B auto-receptors. Whether the auto-receptors in each sub-system are functionally altered in depressive-like state remains unknown. The present study is aimed to study a specific circuit (DR-ventral hippocampus and MR-dorsal hippocampus) within each sub-system to investigate changes in receptor sensitivity in the pathogenesis of depression. A mouse model of depression was developed through the social defeat paradigm, and was then treated with fluoxetine (FLX). 5-HT1A auto-receptor in the neuronal cell body (DR or MR) and 5-HT1B auto-receptor in the axonal terminal (ventral or dorsal hippocampus) were directly targeted by local perfusion of antagonists (5-HT1A: WAY100635; 5-HT1B: GR127935) through reverse microdialysis. Time courses of dialysate 5-HT measured at the axonal terminal were subsequently determined for each circuit. At baseline, 5-HT1A and 5-HT1B antagonists dose-dependently increased dialysate 5-HT, with sub-circuit specificity. In the depressive-like state, greater increases in dialysate 5-HT were observed only in the DR-ventral hippocampus circuit following local delivery of both antagonists, which were then fully restored following the FLX treatment. In contrast, no changes were observed in the MR-dorsal hippocampus circuit. Our results demonstrate differential changes in sensitivities of 5-HT1A and 5-HT1B auto-receptors in the DR-ventral hippocampus and MR-dorsal hippocampus circuits. 5-HT1A and 5-HT1B auto-receptors in the DR-ventral hippocampus circuit are sensitized in the depressive-like state. Taken together, these results suggest that the DR sub-system maybe the neural substrate mediating depressive phenotypes. Copyright © 2020 Elsevier B.V. All rights reserved.

Citation

Xiang Li, Xianan Sun, Jing Sun, Yi Zu, Shulei Zhao, Xiao Sun, Lu Li, Xinjing Zhang, Wei Wang, Yuezhu Liang, Wenyao Wang, Xuankai Liang, Chi Sun, Xue Guan, Man Tang. Depressive-like state sensitizes 5-HT1A and 5-HT1B auto-receptors in the dorsal raphe nucleus sub-system. Behavioural brain research. 2020 Jul 01;389:112618