Contribution of Hippocampal 5-HT3Receptors in Hippocampal Autophagy and Extinction of Conditioned Fear Responses after a Single Prolonged Stress Exposure in Rats.
One of the hypotheses about the pathogenesis of posttraumatic stress disorder (PTSD) is the dysfunction of serotonin (5-HT) neurotransmission. While certain 5-HT receptor subtypes are likely critical for the symptoms of PTSD, few studies have examined the role of 5-HT3receptor in the development of PTSD, even though 5-HT3receptor is critical for contextual fear extinction and anxiety-like behavior. Therefore, we hypothesized that stimulation of 5-HT3receptor in the dorsal hippocampus (DH) could prevent hippocampal autophagy and the development of PTSD-like behavior in animals. To this end, we infused SR57227, selective 5-HT3agonist, into the DH after a single prolonged stress (SPS) treatment in rats. Three weeks later, we evaluated the effects of this pharmacological treatment on anxiety-related behaviors and extinction of contextual fear memory. We also accessed hippocampal autophagy and the expression of 5-HT3Asubunit, Beclin-1, LC3-I, and LC3-II in the DH. We found that SPS treatment did not alter anxiety-related behaviors but prolonged the extinction of contextual fear memory, and such a behavioral phenomenon was correlated with increased hippocampal autophagy, decreased 5-HT3Aexpression, and increased expression of Beclin-1 and LC3-II/LC3-I ratio in the DH. Furthermore, intraDH infusions of SR57227 dose-dependently promoted the extinction of contextual fear memory, prevented hippocampal autophagy, and decreased expression of Beclin-1 and LC3-II/LC3-I ratio in the DH. These results indicated that 5-HT3receptor in the hippocampus may play a critical role in the pathogenesis of hippocampal autophagy, and is likely involved in the pathophysiology of PTSD.
Department of Anatomy, Medical College of Taizhou University, 1139 Taizhou city government Avenue, Taizhou, 318000, China.|Department of Neurology, First People's Hospital of Linhai City, Linhai, 317000, China.
Zhong-Min
ZM
Wu
Department of Neurology, Taizhou Hospital, Taizhou, 317000, China.
Li-Hua
LH
Yang
Department of Neurology, First People's Hospital of Linhai City, Linhai, 317000, China.
Rong
R
Cui
Department of Neurology, First People's Hospital of Linhai City, Linhai, 317000, China.
Gui-Lian
GL
Ni
City College of Zhejiang University, Hangzhou, 310015, China.
Feng-Tian
FT
Wu
Department of Anatomy, Medical College of Taizhou University, 1139 Taizhou city government Avenue, Taizhou, 318000, China. yonggliang@sina.com.
Yong
Y
Liang
D000818:Animals; D001343:Autophagy / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects; D005239:Fear / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D017207:Rats, Sprague-Dawley; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects / Q000378:metabolism*; D058827:Serotonin 5-HT3 Receptor Agonists / Q000494:pharmacology; D013315:Stress, Psychological / Q000188:drug therapy / Q000503:physiopathology
D044406:Receptors, Serotonin, 5-HT3; D058827:Serotonin 5-HT3 Receptor Agonists
5-HT3 receptor; Conditioned fear response; Hippocampal autophagy; Memory extinction; Posttraumatic stress disorder