1. ¹Centre for Basic Psychiatric Research, Aarhus Psychiatric University Hospital, Aarhus, Denmark
2. ²Molecular Psychiatry Unit, Wallenberg Neuroscience Center, Lund, Sweden
3. ³Institute of Pharmacology, Polish Academy of Science, Krakow, Poland

Correspondence: Dr O Wiborg, Centre for Basic Psychiatric Research, Aarhus Psychiatric University Hospital, Skovagervej 2, Risskov 8240, Denmark. Tel: +45 7789 3611; Fax: +45 7789 3549; E-mail: owiborg@post.tele.dk

Received 21 June 2005; Revised 13 December 2005; Accepted 20 December 2005; Published online 8 February 2006.

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.