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Hippocampal cytogenesis correlates to escitalopram-mediated recovery in a chronic mild stress rat model of depression

Jayatissa, Magdalena N.; Bisgaard, Christina; Tingström, Anders LU ; Papp, Mariusz and Wiborg, Ove (2006) In Neuropsychopharmacology 31(11). p.2395-2404
Abstract
From clinical studies it is known that recurrent depressive episodes associate with a reduced hippocampal volume. Conversely, preclinical studies have shown that chronic antidepressant treatment increases hippocampal neurogenesis. Consequently, it has been suggested that a deficit in hippocampal neurogenesis is implicated in the pathophysiology of depression. To study a potential correlation between recovery and hippocampal cytogenesis, we established the chronic mild stress ( CMS) rat model of depression. When rats are subjected to CMS, several depressive symptoms develop, including the major symptom anhedonia. Rats were exposed to stress for 2 weeks and subsequently to stress in combination with antidepressant treatment for 4 consecutive... (More)
From clinical studies it is known that recurrent depressive episodes associate with a reduced hippocampal volume. Conversely, preclinical studies have shown that chronic antidepressant treatment increases hippocampal neurogenesis. Consequently, it has been suggested that a deficit in hippocampal neurogenesis is implicated in the pathophysiology of depression. To study a potential correlation between recovery and hippocampal cytogenesis, we established the chronic mild stress ( CMS) rat model of depression. When rats are subjected to CMS, several depressive symptoms develop, including the major symptom anhedonia. Rats were exposed to stress for 2 weeks and subsequently to stress in combination with antidepressant treatment for 4 consecutive weeks. The behavioral deficit measured in anhedonic animals is a reduced intake of a sucrose solution. Prior to perfusion animals were injected with bromodeoxyuridine ( BrdU), a marker of proliferating cells. Brains were sectioned horizontally and newborn cells positive for BrdU were counted in the dentate gyrus and tracked in a dorsoventral direction. CMS significantly decreased sucrose consumption and cytogenesis in the ventral part of the hippocampal formation. During exposure to the antidepressant escitalopram, given as intraperitoneally dosages of either 5 or 10 mg/kg/day, animals distributed in a bimodal fashion into a group, which recovered ( increase in sucrose consumption), and a subgroup, which refracted treatment ( no increase in sucrose consumption). Chronic treatment with escitalopram reversed the CMS-induced decrease in cytogenesis in the dentate gyrus of the ventral hippocampal formation, but in recovered animals only. Our data show a correlation between recovery from anhedonia, as measured by cessation of behavioral deficits in the CMS model, and an increase in cytogenesis in the dentate gyrus of the ventral hippocampal formation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
neurogenesis, cell proliferation, treatment resistance, escitalopram, hippocampal formation, chronic mild stress, depression
in
Neuropsychopharmacology
volume
31
issue
11
pages
2395 - 2404
publisher
Elsevier
external identifiers
  • wos:000241380900010
  • scopus:33747037628
ISSN
1740-634X
DOI
10.1038/sj.npp.1301041
language
English
LU publication?
yes
id
9ec0ea9e-5fc6-405e-9abc-5f663fef7a44 (old id 386644)
date added to LUP
2007-10-05 14:32:05
date last changed
2019-05-12 03:36:15
@article{9ec0ea9e-5fc6-405e-9abc-5f663fef7a44,
  abstract     = {From clinical studies it is known that recurrent depressive episodes associate with a reduced hippocampal volume. Conversely, preclinical studies have shown that chronic antidepressant treatment increases hippocampal neurogenesis. Consequently, it has been suggested that a deficit in hippocampal neurogenesis is implicated in the pathophysiology of depression. To study a potential correlation between recovery and hippocampal cytogenesis, we established the chronic mild stress ( CMS) rat model of depression. When rats are subjected to CMS, several depressive symptoms develop, including the major symptom anhedonia. Rats were exposed to stress for 2 weeks and subsequently to stress in combination with antidepressant treatment for 4 consecutive weeks. The behavioral deficit measured in anhedonic animals is a reduced intake of a sucrose solution. Prior to perfusion animals were injected with bromodeoxyuridine ( BrdU), a marker of proliferating cells. Brains were sectioned horizontally and newborn cells positive for BrdU were counted in the dentate gyrus and tracked in a dorsoventral direction. CMS significantly decreased sucrose consumption and cytogenesis in the ventral part of the hippocampal formation. During exposure to the antidepressant escitalopram, given as intraperitoneally dosages of either 5 or 10 mg/kg/day, animals distributed in a bimodal fashion into a group, which recovered ( increase in sucrose consumption), and a subgroup, which refracted treatment ( no increase in sucrose consumption). Chronic treatment with escitalopram reversed the CMS-induced decrease in cytogenesis in the dentate gyrus of the ventral hippocampal formation, but in recovered animals only. Our data show a correlation between recovery from anhedonia, as measured by cessation of behavioral deficits in the CMS model, and an increase in cytogenesis in the dentate gyrus of the ventral hippocampal formation.},
  author       = {Jayatissa, Magdalena N. and Bisgaard, Christina and Tingström, Anders and Papp, Mariusz and Wiborg, Ove},
  issn         = {1740-634X},
  keyword      = {neurogenesis,cell proliferation,treatment resistance,escitalopram,hippocampal formation,chronic mild stress,depression},
  language     = {eng},
  number       = {11},
  pages        = {2395--2404},
  publisher    = {Elsevier},
  series       = {Neuropsychopharmacology},
  title        = {Hippocampal cytogenesis correlates to escitalopram-mediated recovery in a chronic mild stress rat model of depression},
  url          = {http://dx.doi.org/10.1038/sj.npp.1301041},
  volume       = {31},
  year         = {2006},
}