PMID- 26337614 OWN - NLM STAT- MEDLINE DCOM- 20160622 LR - 20181202 IS - 1432-2072 (Electronic) IS - 0033-3158 (Linking) VI - 232 IP - 23 DP - 2015 Dec TI - Comparison of ketamine, 7,8-dihydroxyflavone, and ANA-12 antidepressant effects in the social defeat stress model of depression. PG - 4325-35 LID - 10.1007/s00213-015-4062-3 [doi] AB - RATIONALE: Brain-derived neurotrophic factor (BDNF) and signaling at its receptor, tropomyosin-related kinase B (TrkB), are implicated in the rapid and long-lasting antidepressant effects of ketamine. Moreover, a TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF), and/or TrkB antagonist, ANA-12, shows antidepressant effects in animal models of depression. OBJECTIVE: The objective of this study is to compare the influence of ketamine, 7,8-DHF, and ANA-12 on antidepressant activity in the social defeat stress model. RESULTS: In the tail suspension and forced swimming tests, ketamine, 7,8-DHF, or ANA-12 markedly attenuated the increased immobility time in depressed mice compared with the vehicle-treated group. In the sucrose preference test, all drugs significantly improved the reduced preference in depressed mice at both 1 and 3 days after a single dose. Antidepressant effect of ketamine, but not 7,8-DHF or ANA-12, was still detectable 7 days after a single dose. Western blot analyses showed that ketamine, but not 7,8-DHF or ANA-12, markedly attenuated reduced levels of BDNF and postsynaptic density protein 95 (PSD-95) in the prefrontal cortex (PFC), dentate gyrus (DG), and CA3 of the hippocampus in depressed mice 8 days after a single dose. Furthermore, ketamine markedly increased reduced levels of GluA1 in the PFC and DG of depressed mice. In contrast, ketamine showed no effect against increased levels of BDNF, PSD-95, and GluA1 observed in the nucleus accumbens of depressed mice. CONCLUSIONS: Compared with 7,8-DHF and ANA-12, ketamine is a longer-lasting antidepressant in the social defeat stress model, and synaptogenesis may be required for the mechanisms that promote sustained antidepressant effects of ketamine. FAU - Zhang, Ji-chun AU - Zhang JC AD - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan. FAU - Yao, Wei AU - Yao W AD - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan. FAU - Dong, Chao AU - Dong C AD - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan. FAU - Yang, Chun AU - Yang C AD - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan. FAU - Ren, Qian AU - Ren Q AD - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan. FAU - Ma, Min AU - Ma M AD - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan. FAU - Han, Mei AU - Han M AD - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan. FAU - Hashimoto, Kenji AU - Hashimoto K AD - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan. hashimoto@faculty.chiba-u.jp. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150904 PL - Germany TA - Psychopharmacology (Berl) JT - Psychopharmacology JID - 7608025 RN - 0 (6,7-dihydroxyflavone) RN - 0 (ANA 12 compound) RN - 0 (Antidepressive Agents) RN - 0 (Azepines) RN - 0 (Benzamides) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Flavones) RN - 690G0D6V8H (Ketamine) SB - IM MH - Animals MH - Antidepressive Agents/pharmacology/therapeutic use MH - Azepines/pharmacology/*therapeutic use MH - Benzamides/pharmacology/*therapeutic use MH - Brain-Derived Neurotrophic Factor/metabolism MH - Depression/*drug therapy/metabolism/psychology MH - *Disease Models, Animal MH - Flavones/pharmacology/*therapeutic use MH - Hindlimb Suspension/psychology MH - Hippocampus/drug effects/metabolism MH - Ketamine/pharmacology/*therapeutic use MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Nucleus Accumbens/drug effects/metabolism MH - Prefrontal Cortex/drug effects/metabolism MH - Stress, Psychological/*drug therapy/metabolism/psychology MH - Swimming/psychology OTO - NOTNLM OT - AMPA receptor OT - Accumbens OT - Animal model OT - Antidepressant OT - BDNF OT - Dentate gyrus OT - Frontal cortex OT - Glutamate receptor OT - NMDA receptor OT - Stress EDAT- 2015/09/05 06:00 MHDA- 2016/06/23 06:00 CRDT- 2015/09/05 06:00 PHST- 2015/04/24 00:00 [received] PHST- 2015/08/24 00:00 [accepted] PHST- 2015/09/05 06:00 [entrez] PHST- 2015/09/05 06:00 [pubmed] PHST- 2016/06/23 06:00 [medline] AID - 10.1007/s00213-015-4062-3 [pii] AID - 10.1007/s00213-015-4062-3 [doi] PST - ppublish SO - Psychopharmacology (Berl). 2015 Dec;232(23):4325-35. doi: 10.1007/s00213-015-4062-3. Epub 2015 Sep 4.