Chronic mild stress-induced depression-like symptoms in rats and abnormalities in catecholamine uptake in small arteries

Elena V. Bouzinova, Nina Møller-Nielsen, Donna B. Boedtkjer, Torbjoern Broegger, Ove Wiborg, Christian Aalkjaer, Vladimir V. Matchkov*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

21 Citations (Scopus)

Abstract

OBJECTIVE: Major depression and cardiovascular diseases have a strong comorbidity; however, the reason for this is unknown. In the chronic mild stress (CMS) model of depression, only a fraction of rats develop a major feature of depression-anhedonia-like behavior, whereas other rats are stress resilient. Previous studies suggested that CMS rats also have increased total peripheral vascular resistance. METHODS: On the basis of CMS-induced changes of sucrose intake, a reliable measure for anhedonia, rats were divided into "resilient" and "anhedonic" groups. An interaction between hedonic status and vascular function was studied after 4 and 8 weeks of CMS exposure in vitro in wire myograph on saphenous arteries and mesenteric small arteries (MSAs) from these rats. RESULTS: When comparing the different experimental rat groups, arterial sensitivities to noradrenaline (NA) were similar under control conditions, but in the presence of the neuronal reuptake inhibitor cocaine, arteries from anhedonic rats were more sensitive to NA. No change in perivascular innervation was found, but elevated expression of neuronal NA transporter was detected. Inhibition of extraneuronal uptake with corticosterone (1 μM) suggests that this transport is diminished in MSAs after CMS. The corticosterone-sensitive transporter organic cation cotransporter 2 was shown to be reduced in MSAs after CMS. No CMS-induced changes in the corticosterone-sensitive transport were found in saphenous arteries. CONCLUSIONS: Our results indicate that CMS-induced depression-like symptoms in rats are associated with changes in catecholamine uptake pathways in the vascular wall, which potentially modulates the effect of sympathetic innervation of resistance arteries.

Original languageEnglish
JournalPsychosomatic Medicine
Volume74
Issue3
Pages (from-to)278-287
Number of pages10
ISSN0033-3174
DOIs
Publication statusPublished - 1 Jan 2012

Keywords

  • anhedonia and resilience
  • blood pressure
  • cardiovascular disorders
  • catecholamine uptake
  • resistance arteries

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