title: Ziprasidone ameliorates anxiety-like behaviors in a rat model of PTSD and up-regulates neurogenesis in the hippocampus and hippocampus-derived neural stem cells.
abstract: Ziprasidone, a widely used atypical antipsychotic drug, has been demonstrated to have therapeutic effects in patients with post-traumatic stress disorder (PTSD), but its underlying mechanisms remain poorly understood. One possible explanation is that the neuroprotective and neurogenetic actions of ziprasidone can attenuate the neuronal apoptosis which occurs in the hippocampus. To test this hypothesis, the present study was designed to assess the effects of ziprasidone treatment on anxiety-like behaviors, hippocampal neurogenesis, and in vivo/in vitro expression of pERK1/2 and Bcl-2 in male Sprague-Dawley rats. The methodology involved 3 different experiments, and the investigations also included the assessment of U0126 interference in ziprasidone treatment. It was found that the in vivo, administration of ziprasidone not only reversed the anxiety-like behaviors in rats that exposed to an enhanced single prolonged stress paradigm, but also restored the proliferation and the protein expression of pERK1/2 and Bcl-2 in the hippocampus of these rats. Also, mild concentrations of ziprasidone promoted the in vitro proliferation of hippocampal-derived neural stem cells (NSCs) and increased the levels of pERK1/2 and Bcl-2 in NSCs. Interestingly, the observed effects of ziprasidone were inhibited by U0126. These data support the use of ziprasidone for the treatment of PTSD and indicate that the changes in the ERK1/2 signaling cascade may play a critical role in the pathophysiology of PTSD and its treatment modalities. Further investigations are needed to elucidate the detailed signal cascades involved in the pathophysiology of stress-related disorders, and confirm the efficacy of ziprasidone in anti-PTSD treatment.
authors: Department of Psychosomatic Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors: Zhengwu
authors: Z
authors: Peng
authors: Ruiguo
authors: R
authors: Zhang
authors: Huaning
authors: H
authors: Wang
authors: Yunchun
authors: Y
authors: Chen
authors: Fen
authors: F
authors: Xue
authors: Lei
authors: L
authors: Wang
authors: Fan
authors: F
authors: Yang
authors: Yihuan
authors: Y
authors: Chen
authors: Ling
authors: L
authors: Liu
authors: Fang
authors: F
authors: Kuang
authors: Qingrong
authors: Q
authors: Tan
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D002070:Butadienes / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects*; D055495:Neurogenesis / Q000187:drug effects*; D009570:Nitriles / Q000494:pharmacology; D010879:Piperazines / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D013844:Thiazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D014151:Anti-Anxiety Agents; D002070:Butadienes; D009570:Nitriles; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D013844:Thiazoles; C113580:U 0126; C092292:ziprasidone