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Increased numbers of orexin/hypocretin neurons in a genetic rat depression model.

Mikrouli, Elli; Wörtwein, Gitta; Soylu, Rana LU ; Mathe, Aleksander A and Petersén, Åsa LU (2011) In Neuropeptides 45. p.401-406
Abstract
The Flinders Sensitive Line (FSL) rat is a genetic animal model of depression that displays characteristics similar to those of depressed patients including lower body weight, decreased appetite and reduced REM sleep latency. Hypothalamic neuropeptides such as orexin/hypocretin, melanin-concentrating hormone (MCH) and cocaine and amphetamine regulated transcript (CART), that are involved in the regulation of both energy metabolism and sleep, have recently been implicated also in depression. We therefore hypothesized that alterations in these neuropeptide systems may play a role in the development of the FSL phenotype with both depressive like behavior, metabolic abnormalities and sleep disturbances. In this study, we first confirmed that... (More)
The Flinders Sensitive Line (FSL) rat is a genetic animal model of depression that displays characteristics similar to those of depressed patients including lower body weight, decreased appetite and reduced REM sleep latency. Hypothalamic neuropeptides such as orexin/hypocretin, melanin-concentrating hormone (MCH) and cocaine and amphetamine regulated transcript (CART), that are involved in the regulation of both energy metabolism and sleep, have recently been implicated also in depression. We therefore hypothesized that alterations in these neuropeptide systems may play a role in the development of the FSL phenotype with both depressive like behavior, metabolic abnormalities and sleep disturbances. In this study, we first confirmed that the FSL rats displayed increased immobility in the Porsolt forced swim test compared to their control strain, the Flinders Resistant Line (FRL), which is indicative of depressive-like behavior. We then examined the number of orexin-, MCH- and CART-immunopositive neurons in the hypothalamus using stereological analyses. We found that the total number of orexin-positive neurons was higher in the hypothalamus of female FSL rats compared to female FRL rats, whereas no changes in the MCH or CART populations could be detected between the strains. Chronic treatment with the selective serotonin reuptake inhibitor (SSRI) escitalopram reduced immobility only in the FRL rats where it also increased the number of MCH positive neurons compared to untreated rats. These findings support the view that orexin may be involved in depression and strengthen the notion that the "depressed" brain responds differently to pharmacological interventions than the normal brain. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Neuropeptides
volume
45
pages
401 - 406
publisher
Elsevier
external identifiers
  • WOS:000297875400006
  • PMID:21871662
  • Scopus:83355166842
ISSN
1532-2785
DOI
10.1016/j.npep.2011.07.010
language
English
LU publication?
yes
id
99f0cf18-8821-4faf-b75b-df1d91ddcbcd (old id 2150655)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21871662?dopt=Abstract
date added to LUP
2011-09-04 12:57:40
date last changed
2017-01-01 07:51:47
@article{99f0cf18-8821-4faf-b75b-df1d91ddcbcd,
  abstract     = {The Flinders Sensitive Line (FSL) rat is a genetic animal model of depression that displays characteristics similar to those of depressed patients including lower body weight, decreased appetite and reduced REM sleep latency. Hypothalamic neuropeptides such as orexin/hypocretin, melanin-concentrating hormone (MCH) and cocaine and amphetamine regulated transcript (CART), that are involved in the regulation of both energy metabolism and sleep, have recently been implicated also in depression. We therefore hypothesized that alterations in these neuropeptide systems may play a role in the development of the FSL phenotype with both depressive like behavior, metabolic abnormalities and sleep disturbances. In this study, we first confirmed that the FSL rats displayed increased immobility in the Porsolt forced swim test compared to their control strain, the Flinders Resistant Line (FRL), which is indicative of depressive-like behavior. We then examined the number of orexin-, MCH- and CART-immunopositive neurons in the hypothalamus using stereological analyses. We found that the total number of orexin-positive neurons was higher in the hypothalamus of female FSL rats compared to female FRL rats, whereas no changes in the MCH or CART populations could be detected between the strains. Chronic treatment with the selective serotonin reuptake inhibitor (SSRI) escitalopram reduced immobility only in the FRL rats where it also increased the number of MCH positive neurons compared to untreated rats. These findings support the view that orexin may be involved in depression and strengthen the notion that the "depressed" brain responds differently to pharmacological interventions than the normal brain.},
  author       = {Mikrouli, Elli and Wörtwein, Gitta and Soylu, Rana and Mathe, Aleksander A and Petersén, Åsa},
  issn         = {1532-2785},
  language     = {eng},
  pages        = {401--406},
  publisher    = {Elsevier},
  series       = {Neuropeptides},
  title        = {Increased numbers of orexin/hypocretin neurons in a genetic rat depression model.},
  url          = {http://dx.doi.org/10.1016/j.npep.2011.07.010},
  volume       = {45},
  year         = {2011},
}