title: Anxiolytic effects of ketamine in animal models of posttraumatic stress disorder.
abstract: This study investigated the effectiveness of ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, in alleviating the enhanced anxiety and fear response in both a mouse model of PTSD induced by inescapable electric foot shocks and a rat model of PTSD induced by a time-dependent sensitization (TDS) procedure. First, we evaluated the effect of ketamine on behavioral deficits in a mouse model of PTSD that consisted of foot shocks followed by three situational reminders. Our results showed that the aversive procedure induced several behavioral deficiencies, such as increased freezing behavior and anxiety, as well as reduced time spent in an aversive-like context, which were reversed by repeated treatment with ketamine. The effect of ketamine on behavioral changes after exposure to TDS was also investigated, and the levels of brain-derived neurotrophic factor (BDNF) in the hippocampus were measured. The results revealed that after TDS, the rats showed a significant increase in contextual freezing and a decrease in the percentage of time spent in and numbers of entries into open arms in the elevated plus maze test. As a positive control drug, sertraline (Ser, 15 mg/kg, i.g.), a selective serotonin reuptake inhibitor (SSRI) ameliorated these behavioral deficits. These behavioral effects were mimicked by chronic ketamine treatment. Furthermore, ketamine normalized the decreased BDNF level in the hippocampus in post-TDS rats. Taken together, these results suggest that ketamine exerts a therapeutic effect on PTSD that might be at least partially mediated by an influence on BDNF signaling in the hippocampus.
authors.affiliation: Department of New Drug Evaluation, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Haidian, Beijing, 100850, China.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Zhang
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Zhou
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Ji
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Nan
authors.initials: N
authors.lastname: Zhao
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Chen
authors.forename: Rui
authors.initials: R
authors.lastname: Xue
authors.forename: Xin-Guo
authors.initials: XG
authors.lastname: Mei
authors.forename: You-Zhi
authors.initials: YZ
authors.lastname: Zhang
authors.forename: Heng-Lin
authors.initials: HL
authors.lastname: Wang
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Li
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D014151:Anti-Anxiety Agents; D019208:Brain-Derived Neurotrophic Factor; D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine