title: Chronic treatment with tandospirone, a serotonin 1A receptor partial agonist, inhibits psychosocial stress-induced changes in hippocampal neurogenesis and behavior.
abstract: BACKGROUND
  The 5-hydroxytryptamine (5-HT) 1A receptors are considered a potential target for the treatment of mental and neuropsychiatric disorders. Several studies have indicated that 5-HT1A receptor agonists increase hippocampal neurogenesis, which is implicated in the action mechanism of antidepressants. However, these agents have not been applied to humans due to intolerable side effects. We recently showed that chronic administration of tandospirone, a clinically available 5-HT1A receptor partial agonist, increased hippocampal neurogenesis dose-dependently. The present study was done to determine if chronic tandospirone treatment has antidepressant potential from the standpoint of hippocampal neurogenesis and behavior.
  
  
  METHODS
  Male Sprague-Dawley rats were intraperitoneally administered a vehicle or tandospirone (10mg/kg) once daily for 28 days. Two weeks after starting the injections, animals were exposed to intermittent social defeat (four times over two weeks). The effects of stress and tandospirone on the rodents׳ behavior were evaluated by the Novelty-Suppressed Feeding (NSF) test. The quantification of hippocampal neurogenesis was estimated using immunostaining with Ki-67 and doublecortin (DCX).
  
  
  RESULTS
  Chronic tandospirone treatment reversed the psychosocial stress-induced increase in the latency in the NSF test and decrease in the density of DCX-positive cells in the dentate gyrus of the dorsal and ventral hippocampus. However, no difference in the density of Ki-67-positive cells was observed between the vehicle- and tandospirone-administered groups.
  
  
  CONCLUSIONS
  To clarify the antidepressant potential of TDS, the other behavioral tests for depression will be required.
  
  
  CONCLUSIONS
  Our findings suggest that tandospirone has antidepressant potential through an inhibiting effect on stress-induced changes in hippocampal neurogenesis.
authors: Department of Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. Electronic address: ymurata@fukuoka-u.ac.jp.
authors: Yusuke
authors: Y
authors: Murata
authors: Department of Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
authors: Yuki
authors: Y
authors: Yanagihara
authors: Department of Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
authors: Masayoshi
authors: M
authors: Mori
authors: Faculty of Neurology and Psychiatry, Mito Hospital, 4-1-1, Shime-Higashi, Shime-Machi, Kasuya-Gun, Fukuoka 811-2243, Japan.
authors: Kazunori
authors: K
authors: Mine
authors: Department of Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
authors: Munechika
authors: M
authors: Enjoji
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000187:drug effects; D003866:Depressive Disorder / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004334:Drug Administration Schedule; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D007267:Injections; D054833:Isoindoles / Q000008:administration & dosage / Q000494:pharmacology*; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis; D055495:Neurogenesis / Q000187:drug effects*; D009479:Neuropeptides / Q000032:analysis; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000378:metabolism*; D012107:Research Design; D058825:Serotonin 5-HT1 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D012919:Social Behavior; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; C000714328:DCX protein, human; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D054833:Isoindoles; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D010879:Piperazines; D011743:Pyrimidines; D058825:Serotonin 5-HT1 Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; C055267:tandospirone
keywords: Antidepressant; Hippocampal neurogenesis; Novelty-Suppressed Feeding test; Serotonin 1A receptor partial agonist; Social defeat; Tandospirone