Hippocampal Cytogenesis Correlates to Escitalopram-Mediated Recovery in a Chronic Mild Stress Rat Model of Depression
by
Jayatissa MN, Bisgaard C, Tingstrom A, Papp M, Wiborg O.
1Centre for Basic Psychiatric Research,
Aarhus Psychiatric University Hospital,
Aarhus, Denmark.
Neuropsychopharmacology. 2006 Feb 8;


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
Neurogenesis
Escitalopram (Lexapro)
Citalopram and ecstasy
SSRIs and panic disorder
Citalopram and selegiline
Citalopram v amitriptyline
Citalopram and depression
Citalopram and panic disorder
Serotonin and romantic lovers
Citalopram and eating disorders
Citalopram maintenance therapy
Citalopram and depression: trials
Big Pharma meets Madison Avenue
Citalopram: oral versus intravenous
Serotonin and the genetics of depression
Single isomer SSRI escitalopram as an antidepressant
Escitalopram (Lexapro) : mechanism of antidepressant action


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