Effects of chronic mild stress on sexual behavior, locomotor activity and consumption of sucrose and saccharine solutions

Grønli, Janne; Murison, Robert; Fiske, Eldbjørg; Bjorvatn, Bjørn; Sørensen, Eli; Portas, Chiara M.; Ursin, Reidun

doi:10.1016/j.physbeh.2005.02.007

Cited by 272 publications

(144 citation statements)

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“…In accordance with previous results (30,32,33), CMSsusceptible rats showed an increased locomotor activity. Although the locomotor activity was not affected by escitalopram treatment, an anxiolytic-like effect and increased explorative behavior were observed in escitalopram responders (Fig.…”

Section: Discussionsupporting

confidence: 93%

Chronic selective serotonin reuptake inhibition modulates endothelial dysfunction and oxidative state in rat chronic mild stress model of depression

Matchkov

Кравцова

Wiborg

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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Matchkov VV, Kravtsova VV, Wiborg O, Aalkjaer C, Bouzinova EV. Chronic selective serotonin reuptake inhibition modulates endothelial dysfunction and oxidative state in rat chronic mild stress model of depression. Am J Physiol Regul Integr Comp Physiol 309: R814 -R823, 2015. First published August 12, 2015 doi:10.1152/ajpregu.00337.2014.-Major depression is known to be associated with cardiovascular abnormalities, and oxidative stress has been suggested to play a role. We tested the hypothesis that antidepressant treatment reduces oxidative stress and endothelial dysfunctions in the chronic mild stress (CMS) model of depression in rats. Rats with Ͼ30% reduction in sucrose intake after 4 wk of CMS were defined in the study as CMS-susceptible and compared with unstressed controls. Sixteen CMS-susceptible and eight unstressed rats were treated during weeks 5 to 8 of the CMS protocol with escitalopram. Escitalopram-treated rats with Ͼ20% recovery in the sucrose consumption during the last 2 wk of treatment were defined as escitalopram responders. Rats that did not reach these criteria were defined as escitalopram nonresponders. In the open field test, escitalopram responders demonstrated anxiolytic effect of treatment. In mesenteric small arteries, escitalopram affected neither NO nor cyclooxygenase-1 (COX-1)-mediated vasodilation. Escitalopram potentiated endothelium-dependent hyperpolarization-like response, which was suppressed in the vehicle-treated CMS-susceptible rats and reduced COX-2-dependent relaxation, which was elevated in the vehicle-treated CMS-susceptible rats. Escitalopram did not affect blood pressure and heart rate, which were elevated in the vehicle-treated CMS-susceptible rats. Oxidative stress markers were changed in association with CMS in liver, heart, and brain. Escitalopram normalized oxidative stress markers in the majority of tissues. This study demonstrates that the antidepressant effect of escitalopram is associated with partial improvement of endothelial function in small arteries affecting COX-2 and endothelium-dependent hyperpolarization-like pathways.depression; chronic mild stress; escitalopram; endothelium; nitric oxide synthase; cyclooxygenase; endothelium-derived hyperpolarization; oxidative stress; glutathione; malondialdehyde CARDIOVASCULAR DISEASES AND major depressive disorder are the two most prevalent health problems in high-income countries (31). Their comorbidity is well recognized, but the mechanisms and critical factors underlying this comorbidity are unknown. Interactions between several factors common for both disorders are complex (17; 43). Thus, a dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis and activation of the renin-angiotensin-aldosterone system lead to changes associated with both depression and cardiovascular abnormalities.Also dysfunction of the autonomic nervous system (sympathetic/parasympathetic) is known to be involved, as well as an activation of proinflammatory cytokines (46). Importantly, these factors can induce both depression and ch...

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Section: Discussionsupporting

confidence: 93%

Chronic selective serotonin reuptake inhibition modulates endothelial dysfunction and oxidative state in rat chronic mild stress model of depression

Matchkov

Кравцова

Wiborg

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Those animals developing exploratory deficits in response to chronic stress consistently display increased floating during forced swimming and decreased preference for sweet tastes (Berger et al, 2004, behaviors widely used to model depression and anhedonia in rats and mice (Detke et al, 1995, Crowley et al, 2004. Indeed, in the chronic mild stress model of depression in both rats and mice, decrements in both exploratory behavior and reward seeking are prominent features (Willner et al, 1992, Argyropoulos and Nutt, 1997, Bielajew et al, 2002, Anisman and Matheson, 2005, Bekris et al, 2005, Gronli et al, 2005. Similar results have also been reported following chronic social stress (Rygula et al, 2005).…”

Section: Chronic Crf Receptor Agonism In the Drn And Behaviormentioning

confidence: 64%

Chronic low dose ovine corticotropin releasing factor or urocortin II into the rostral dorsal raphe alters exploratory behavior and serotonergic gene expression in specific subregions of the dorsal raphe

et al. 2007

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Corticotropin releasing factor (CRF) family peptides play key roles in integrating neural responses to stress. Both major CRF receptors have been pharmacologically identified in the dorsal raphe nucleus (DRN), a stress sensitive and internally heterogeneous nucleus supplying many forebrain regions with serotonergic input. Despite the involvement of chronic stress and serotonergic dysfunction in human mood and anxiety disorders, little is known about the effects of chronic CRF receptor activation on the DRN. We infused ovine CRF (1ng/hr), urocortin II (UCNII, 1ng/hr), or vehicle alone into rat DRN over 6 days. During infusion, animals were allowed to freely explore an open field for 15 minutes on each of two days, with the addition of a novel object on the second day. Following behavioral testing, 5-HT 1A , 5-HT 1B , serotonin transporter (SERT), and tryptophan hydroxylase-2 (Tph2) expression were examined through the DRN by in situ hybridization. Ovine CRF infusion resulted in significantly decreased novel object touches, climbs, as well as increased latency to first novel object contact. UCNII had a similar but less dramatic effect, decreasing only climbing behavior. Both ovine CRF and UCNII blunted the decrease in corner time expected on reexposure to the open field. Both peptides also produced regionally specific changes in gene expression: 5-HT 1A expression was increased 30% in the mid-rostral ventromedial DRN, while SERT was decreased by 30% in the mid-caudal shell dorsomedial DRN. There also appeared to be a shift in the relative level of Tph2 expression between the ventromedial and core dorsomedial DRN at the mid-rostral level. Changes in 5-HT 1A , SERT, and relative Tph2 mRNA abundance were correlated with novel object exploration. These findings suggest chronic intra-DRN administration of CRF agonists decreases exploratory behavior, while producing subregionally limited changes in serotonergic gene expression. These studies may be relevant to mechanisms underlying behavioral changes after chronic stress. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptDepression and anxiety disorders are among the leading causes of morbidity, mortality, and disability in the United States (Greenberg et al., 2003). They are often comorbid, and both are highly associated with chronic exposure to stress. Multiple lines of evidence suggest that chronic and inescapable stress produce long lasting effects on brain function and behavior that play a prominent role in the development, maintenance, and recurrence of both depression and a variety of anxiety disorders (Gulley and Nemeroff, 1993, Arborelius et al., 1999, Ressler and Nemeroff, 2000.Altered serotonin neurotransmission appears to be a central mechanism inducing both depressive (Maes and Meltzer, 1995) and anxiety disorders (Ressler and Nemeroff, 2000). The majority of serotonergic fibers to forebrain regions thought to be involved in mood and anxiety regulation arise from the dorsal raphe nucleus (DRN) and median raphe nucleus (MRN) ...

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“…Moreover, mice lacking an isoform of GAD65 have shown reduced GABA levels and increased anxiety (46,47) while rats exposed to CMS show reduced GABA levels, anhedonia and helplessness (48,49). We suggest that the downregulation of VGAT and its coupled GABA synthesising enzyme GAD65 in response to CMS could explain the decreased GABA levels observed in the frontal cortex and in the hippocampus of the CMS mice.…”

Section: Regulation Of Glutamate/gaba Cycle and Behaviour By Cms In Wmentioning

confidence: 80%

Increased Vulnerability to Depressive-Like Behavior of Mice with Decreased Expression of VGLUT1

Garcia-García

Elizalde

Matrov

et al. 2009

Biological Psychiatry

114

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Effects of chronic mild stress on sexual behavior, locomotor activity and consumption of sucrose and saccharine solutions

Cited by 272 publications

References 40 publications

Chronic selective serotonin reuptake inhibition modulates endothelial dysfunction and oxidative state in rat chronic mild stress model of depression

Chronic selective serotonin reuptake inhibition modulates endothelial dysfunction and oxidative state in rat chronic mild stress model of depression

Chronic low dose ovine corticotropin releasing factor or urocortin II into the rostral dorsal raphe alters exploratory behavior and serotonergic gene expression in specific subregions of the dorsal raphe

Increased Vulnerability to Depressive-Like Behavior of Mice with Decreased Expression of VGLUT1

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