title: Chronic mild stress-induced depression-like symptoms in rats and abnormalities in catecholamine uptake in small arteries.
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.
authors.affiliation: Center for Psychiatric Research, Aarhus University Hospital, Denmark.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Bouzinova
authors.forename: Nina
authors.initials: N
authors.lastname: Møller-Nielsen
authors.forename: Donna B
authors.initials: DB
authors.lastname: Boedtkjer
authors.forename: Torbjoern
authors.initials: T
authors.lastname: Broegger
authors.forename: Ove
authors.initials: O
authors.lastname: Wiborg
authors.forename: Christian
authors.initials: C
authors.lastname: Aalkjaer
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Matchkov
mesh_terms: D000704:Analysis of Variance; D059445:Anhedonia / Q000502:physiology; D000818:Animals; D001158:Arteries / Q000294:innervation / Q000378:metabolism* / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002395:Catecholamines / Q000378:metabolism; D002908:Chronic Disease; D003042:Cocaine / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology; D003863:Depression / Q000378:metabolism / Q000503:physiopathology*; D003866:Depressive Disorder; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000502:physiology; D008297:Male; D009213:Myography; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D055500:Resilience, Psychological; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology*; D013395:Sucrose; D014655:Vascular Resistance / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D002395:Catecholamines; D018765:Dopamine Uptake Inhibitors; D050484:Norepinephrine Plasma Membrane Transport Proteins; D013395:Sucrose; D003042:Cocaine; D003345:Corticosterone; D009638:Norepinephrine