title: Antidepressant-like effects of long-term sarcosine treatment in rats with or without chronic unpredictable stress.
abstract: Sarcosine, an N-methyl-d-aspartate receptor enhancer, can improve depression-like behavior in rodent models and depression in humans. We found that a single dose of sarcosine exerted antidepressant-like effects with rapid concomitant increases in the mammalian target of rapamycin (mTOR) signaling pathway activation and enhancement of α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor (AMPAR) membrane insertion. Sarcosine may play a crucial role in developing novel therapy for depression. For a detailed understanding of sarcosine, this study examined the effects of long-term sarcosine treatment on the forced swim test (FST), mTOR signaling, and AMPAR membrane insertion in rats. The effects of long-term sarcosine treatment were examined in naive rats and rats exposed to chronic unpredictable stress (CUS). Long-term sarcosine treatment (560mg/kg/d for 21 d) significantly ameliorated the increased immobility induced by CUS in the FST, reaffirming the potential role of sarcosine as an antidepressant for depressed patients. The same long-term treatment exhibited no such effect in naive rats despite increased mTOR activation and AMPAR membrane insertion in both groups. Our findings clearly show CUS-exposed rats are sensitive to long-term sarcosine treatment in FST and the response at the same dose is absent in naïve rats. Nevertheless, the distinct sensitivity to long-term sarcosine treatment in rats with or without CUS is not associated with the activated mTOR signaling pathway or increased AMPAR membrane insertion. Additionally, understanding the behavioral and molecular basis of distinct responses is vital important for developing personalized treatment programs to increase the probability of success when treating depression.
authors.affiliation: Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Kuang-Ti
authors.initials: KT
authors.lastname: Chen
authors.affiliation: Department of Anatomy, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ching-Hsiang
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Department of Anatomy, China Medical University, Taichung, Taiwan.
authors.forename: Mang-Hung
authors.initials: MH
authors.lastname: Tsai
authors.affiliation: Department of Nursing, Ching-Kuo Institute of Management and Health, Keelung, Taiwan.
authors.forename: Ya-Chieh
authors.initials: YC
authors.lastname: Wu
authors.affiliation: School of Chinese medicine for post baccalaureate, I Shou University, Kaohsiung, Taiwan.
authors.forename: Ming-Jia
authors.initials: MJ
authors.lastname: Jou
authors.affiliation: Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan; Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; Department of Psychiatry, China Medical University, Taichung, Taiwan. Electronic address: chihchiahuang@yahoo.com.tw.
authors.forename: Chih-Chia
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Department of Anatomy, China Medical University, Taichung, Taiwan. Electronic address: ihwei@mail.cmu.edu.tw.
authors.forename: I-Hua
authors.initials: IH
authors.lastname: Wei
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000209:etiology*; D004195:Disease Models, Animal; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism; D012521:Sarcosine / Q000627:therapeutic use*; D013315:Stress, Psychological / Q000150:complications*; D013550:Swimming / Q000523:psychology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000928:Antidepressive Agents; D018091:Receptors, AMPA; D012521:Sarcosine; D058570:TOR Serine-Threonine Kinases
keywords: AMPA; Depression; Long-term treatment; Sarcosine; mTOR