Decreased cell proliferation in the dentate gyrus does not associate with development of anhedonic-like symptoms in rats.
Depressive disorders have been proposed to be caused by stress-induced down-regulation of hippocampal neurogenesis. Nevertheless, several reports have recently pointed out that, in rodent models of depression, suppression of generation of new hippocampal neurons is not by itself sufficient to induce the development of depression-related symptoms. In the present study, we used the cell proliferation blocker methylazoxymethanol (MAM) and the rat chronic mild stress (CMS) model of depression to challenge the neurogenic theory of depression. In order to achieve a comparable reduction in hippocampal cytogenesis, rats were either chronically treated with MAM for 2 weeks, or subjected to an 8 week regime of chronic mild stress. Consumption of a palatable sucrose solution was monitored once a week to assess the development of anhedonic behavior. Prior to terminal perfusion, the animals were injected with bromodeoxyuridine, a marker of proliferating cells. The number of proliferating cells and total cell number and volume were estimated for the granule cell layer of the ventral hippocampal formation. Unlike CMS, chronic injections with MAM did not induce anhedonia-like symptoms in rats. Both MAM-treated and CMS-exposed groups of rats showed a comparable significant reduction in cell proliferation in the granular cell layer of the ventral hippocampal formation. However, the total cell number was reduced for CMS-exposed rats only while the granule cell layer volume was conserved for both groups. Our results show that suppression of cell proliferation in the hippocampal formation is not an absolute factor for induction of an anhedonia-like state in rats. However, it may still represent an important causal factor for vulnerable subjects.
Jayatissa
M N
MN
Centre for Psychiatric Research, Aarhus University Hospital, Skovagervej 2, 8240 Risskov, Aarhus, Denmark.
Henningsen
K
K
West
M J
MJ
Wiborg
Ove
O
D000477:Alkylating Agents / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D005455:Fluorescent Antibody Technique; D008297:Male; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000502:physiology; D013315:Stress, Psychological / Q000503:physiopathology
D000477:Alkylating Agents; D008746:Methylazoxymethanol Acetate; C030667:methylazoxymethanol