PMID- 24520403 OWN - NLM STAT- MEDLINE DCOM- 20141013 LR - 20211203 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 2 DP - 2014 TI - Preclinical evidence of rapid-onset antidepressant-like effect in Radix Polygalae extract. PG - e88617 LID - 10.1371/journal.pone.0088617 [doi] LID - e88617 AB - Radix Polygalae (the root of Polygala tenuifolia) is a herb widely used in traditional Asian medicine that is thought to exert a variety of neuropsychiatric effects. Radix Polygalae extract can protect against N-methyl D-aspartate (NMDA) neurotoxicity and induce brain-derived neurotrophic factor (BDNF) expression, suggesting modulatory roles at glutamatergic synapses and possible antidepressant action. In accordance with this hypothesis, Radix Polygalae extract demonstrated antidepressant-like effects in 8-week-old male C57Bl/6 mice by decreasing behavioral despair in the forced swim and tail suspension tasks and increasing hedonic-like behavior in the female urine sniffing test 30 minutes after a single oral administration of 0.1 mg/kg. Reduced latency to acquire a food pellet in the novely suppressed feeding paradigm, without change in anxiety-like behaviors suggested a rapid-onset nature of the antidepressant-like effect. In addition, it decreased the number of failed escapes in the learned helplessness paradigm after two oral administrations 24 hours and 30 minutes before the first test. Finally, it reversed anhedonia as measured by saccharin preference in mice exposed to the chronic stress model after two administrations of 0.1 mg/kg, in contrast to the repeated administration generally needed for similar effect by monoamergic antidepressants. Immobility reduction in tail suspension task was blocked by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist NBQX, a pattern previously demonstrated by ketamine and other ketamine-like rapid-onset antidepressants. Also similarly to ketamine, Radix Polygalae appeared to acutely decrease phosphorylation of GluR1 serine-845 in the hippocampus while leaving the phosphorylation of hippocampal mTOR serine 2448 unchanged. These findings serve as preclinical evidence that Radix Polygalae extract exerts rapid-onset antidepressant effects by modulating glutamatergic synapses in critical brain circuits of depression and may be worthy of further evaluation as a safe substitute to other rapid-onset antidepressants known to have unacceptable side effects. FAU - Shin, Im-Joon AU - Shin IJ AD - Department of Applied Korean Medicine, College of Oriental Medicine, Kyung Hee University, Seoul, Korea. FAU - Son, Sung Un AU - Son SU AD - Department of East-West Medicine, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Korea. FAU - Park, Hyunwoo AU - Park H AD - Department of East-West Medicine, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Korea. FAU - Kim, Yoorim AU - Kim Y AD - Department of East-West Medicine, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Korea. FAU - Park, Sung Hyun AU - Park SH AD - Department of East-West Medicine, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Korea. FAU - Swanberg, Kelley AU - Swanberg K AD - Department of East-West Medicine, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Korea. FAU - Shin, Joo-Yeon AU - Shin JY AD - Department of East-West Medicine, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Korea. FAU - Ha, Sang-Kyu AU - Ha SK AD - Department of East-West Medicine, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Korea. FAU - Cho, Yoonju AU - Cho Y AD - Department of Applied Korean Medicine, College of Oriental Medicine, Kyung Hee University, Seoul, Korea. FAU - Bang, Soo-Yong AU - Bang SY AD - Department of East-West Medicine, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Korea. FAU - Lew, Jae-Hwan AU - Lew JH AD - Department of East-West Medicine, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Korea. FAU - Cho, Seung-Hun AU - Cho SH AD - Department of Neuropsychiatry, College of Oriental Medicine, Kyung Hee University, Seoul, Korea. FAU - Maeng, Sungho AU - Maeng S AD - Department of East-West Medicine, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140210 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Antidepressive Agents) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Glutamates) RN - 0 (Plant Extracts) RN - 0 (Protein Subunits) RN - 0 (Receptors, AMPA) RN - 0 (yuan zhi) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - TFZ3H25BS1 (glutamate receptor ionotropic, AMPA 1) SB - IM MH - Animals MH - Antidepressive Agents/pharmacology/*therapeutic use MH - Behavior, Animal/drug effects MH - Chronic Disease MH - Depression/*drug therapy MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Drugs, Chinese Herbal/pharmacology/*therapeutic use MH - Female MH - Glutamates/metabolism MH - Hippocampus/drug effects/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Inbred ICR MH - Phosphorylation/drug effects MH - Phytotherapy MH - Plant Extracts/pharmacology/*therapeutic use MH - Protein Subunits/metabolism MH - Receptors, AMPA/metabolism MH - Stress, Psychological/drug therapy MH - Synapses/drug effects/metabolism MH - TOR Serine-Threonine Kinases/metabolism MH - Time Factors PMC - PMC3919798 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/02/13 06:00 MHDA- 2014/10/14 06:00 PMCR- 2014/02/10 CRDT- 2014/02/13 06:00 PHST- 2013/02/04 00:00 [received] PHST- 2013/12/22 00:00 [accepted] PHST- 2014/02/13 06:00 [entrez] PHST- 2014/02/13 06:00 [pubmed] PHST- 2014/10/14 06:00 [medline] PHST- 2014/02/10 00:00 [pmc-release] AID - PONE-D-13-06314 [pii] AID - 10.1371/journal.pone.0088617 [doi] PST - epublish SO - PLoS One. 2014 Feb 10;9(2):e88617. doi: 10.1371/journal.pone.0088617. eCollection 2014.