title: Piromelatine ameliorates memory deficits associated with chronic mild stress-induced anhedonia in rats.
abstract: Previous studies have demonstrated that piromelatine (a melatonin and serotonin 5-HT1A and 5-HT1D agonist) exerts an antidepressant activity in rodent models of acute stress and improves cognitive impairments in a rat model of Alzheimer's disease (AD). However, the role of piromelatine in chronic stress-induced memory dysfunction remains unclear.
  
  
  
  The aim of this study was to determine whether piromelatine ameliorates chronic mild stress (CMS)-induced memory deficits and explore the underlying mechanisms.
  
  
  
  Rats were exposed randomly to chronic mild stressors for 7 weeks to induce anhedonia (reflected by a significant decrease in sucrose intake), which was used to select rats vulnerable (CMS-anhedonic, CMSA) or resistant (CMS-resistant, CMSR) to stress. Piromelatine (50 mg/kg) was administered daily during the last 2 weeks of CMS. The tail suspension and forced swimming tests were adopted to further characterize vulnerable and resilient rats. The Y-maze and novel object recognition (NOR) tests were used to evaluate memory performance. Brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), phosphorylated CREB (pCREB), and cytogenesis were measured in the hippocampus.
  
  
  
  We found that only CMSA rats displayed significant increases in immobility time in the tail suspension and forced swimming tests; memory deficits in the Y-maze and NOR tests; significant decreases in hippocampal BDNF, CREB, and pCREB expression; and cytogenesis. All these anhedonia-associated effects were reversed by piromelatine.
  
  
  
  Piromelatine ameliorates memory deficits associated with CMS-induced anhedonia in rats and this effect may be mediated by restoring hippocampal BDNF, CREB, and cytogenesis deficits.
authors.affiliation: Department of Neurology, First Affiliated Hospital, University of South China, Hengyang, Hunan, 421001, People's Republic of China.
authors.forename: Wan
authors.initials: W
authors.lastname: Fu
authors.affiliation: Department of Neurology, First Affiliated Hospital, University of South China, Hengyang, Hunan, 421001, People's Republic of China.
authors.forename: Heng
authors.initials: H
authors.lastname: Xie
authors.affiliation: Neurim Pharmaceuticals Ltd., Tel-Aviv, Israel.
authors.forename: Moshe
authors.initials: M
authors.lastname: Laudon
authors.affiliation: Department of Physiology, Medical School, University of South China, Hengyang, 421001, Hunan, People's Republic of China.|Institute of Neuroscience, College of Medicine, University of South China, Hengyang, Hunan, 421001, People's Republic of China.
authors.forename: Shouhong
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Physiology, Medical School, University of South China, Hengyang, 421001, Hunan, People's Republic of China. tsw.neuro@126.com.|Institute of Neuroscience, College of Medicine, University of South China, Hengyang, Hunan, 421001, People's Republic of China. tsw.neuro@126.com.
authors.forename: Shaowen
authors.initials: S
authors.lastname: Tian
authors.affiliation: Department of Neurology, First Affiliated Hospital, University of South China, Hengyang, Hunan, 421001, People's Republic of China. youyong2000@126.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: You
mesh_terms: D059445:Anhedonia / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D011714:Pyrans / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D007211:Indoles; D011714:Pyrans; D058825:Serotonin 5-HT1 Receptor Agonists; C581609:N-(2-(5-methoxy-indol-3-yl)-ethyl)-4-oxo-4H-pyran-2-carboxamide
keywords: BDNF; CREB; Chronic mild stress; Memory deficits; Neurogenesis; Piromelatine