title: Oxotremorine treatment restores hippocampal neurogenesis and ameliorates depression-like behaviour in chronically stressed rats.
abstract: BACKGROUND
  Chronic stress results in cognitive impairment, affects hippocampal neurogenesis and is known to precipitate affective disorders such as depression. In addition to stress, neurotransmitters such as acetylcholine (ACh) modulate adult neurogenesis. Earlier, we have shown that oxotremorine, a cholinergic muscarinic agonist, ameliorates stress-induced cognitive impairment and restores cholinergic function.
  
  
  OBJECTIVE
  In the current study, we have looked into the possible involvement of adult neurogenesis in cognitive restoration by oxotremorine. Further, we have assessed the effect of oxotremorine treatment on depression-like behaviour and hippocampal volumes in stressed animals.
  
  
  METHODS
  Chronic restraint stressed rats were treated with either vehicle or oxotremorine. For neurogenesis studies, proliferation, survival and differentiation of the progenitor cells in the hippocampus were examined using 5'-bromo-2-deoxyuridine immunohistochemistry. Depression-like behaviour was evaluated using forced swim test (FST) and sucrose consumption test (SCT). Volumes were estimated using Cavalieri's estimator.
  
  
  RESULTS
  Hippocampal neurogenesis was severely decreased in stressed rats. Ten days of oxotremorine treatment to stressed animals partially restored proliferation and survival, while it completely restored the differentiation of the newly formed cells. Stressed rats showed increased immobility and decreased sucrose preference in the FST and SCT, respectively, and oxotremorine ameliorated this depression-like behaviour. In addition, oxotremorine treatment recovered the stress-induced decrease in hippocampal volume.
  
  
  CONCLUSIONS
  These results indicate that the restoration of impaired neurogenesis and hippocampal volume could be associated with the behavioural recovery by oxotremorine. Our results imply the muscarinic regulation of adult neurogenesis and incite the potential utility of cholinomimetics in ameliorating cognitive dysfunction in stress-related disorders.
authors.affiliation: Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences (NIMHANS), Hosur Road, PB # 2900, Bangalore, 560 029, India.
authors.forename: J
authors.initials: J
authors.lastname: Veena
authors.forename: B N
authors.initials: BN
authors.lastname: Srikumar
authors.forename: K
authors.initials: K
authors.lastname: Mahati
authors.forename: T R
authors.initials: TR
authors.lastname: Raju
authors.forename: B S
authors.initials: BS
authors.lastname: Shankaranarayana Rao
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D018721:Muscarinic Agonists / Q000627:therapeutic use*; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010095:Oxotremorine / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D013550:Swimming / Q000523:psychology
chemical_list: D018721:Muscarinic Agonists; D010095:Oxotremorine