The antidepressant effects of running and escitalopram are associated with levels of hippocampal NPY and Y1 receptor but not cell proliferation in a rat model of depression

• Published in: Hippocampus Vol. 20; no. 7; pp. 820 - 828
• Main Authors: Bjornebekk, A, Mathe, AA, Brene, S
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.2010
• Subjects: Animals; Antidepressive Agents - pharmacology; Bromodeoxyuridine; Cell Proliferation; Citalopram - pharmacology; depression; Depression - metabolism; Depression - physiopathology; Depression - therapy; Disease Models, Animal; exercise; Female; Hippocampus - metabolism; Hippocampus - physiopathology; Immunohistochemistry; In Situ Hybridization; Medicin och hälsovetenskap; Motor Activity - physiology; neurogenesis; Neuronal Plasticity - drug effects; Neuronal Plasticity - physiology; neuropeptide Y; Neuropeptide Y - biosynthesis; Neuropeptide Y - drug effects; Rats; Receptors, Neuropeptide Y - biosynthesis; Receptors, Neuropeptide Y - drug effects; RNA, Messenger - analysis; Running; SSRI
• ISSN: 1050-9631; 1098-1063; 1098-1063
• DOI: 10.1002/hipo.20683

One hypothesis of depression is that it is caused by reduced neuronal plasticity including hippocampal neurogenesis. In this study, we compared the effects of three long‐term antidepressant treatments: escitalopram, voluntary running, and their combination on hippocampal cell proliferation, NPY and the NPY‐Y1 receptor mRNAs, targets assumed to be important for hippocampal plasticity and mood disorders. An animal model of depression, the Flinders Sensitive Line (FSL) rat, was used and female rats were chosen because the majority of the depressed population is females. We investigated if these treatments were correlated to immobility, swimming, and climbing behaviors, which are associated with an overall, serotonergic‐like and noradrenergic‐like antidepressant response, in the Porsolt swim test (PST). Interestingly, while escitalopram, running and their combination increased the number of hippocampal BrdU immunoreactive cells, the antidepressant‐like effect was only detected in the running group and the group with access both to running wheel and escitalopram. Hippocampal NPY mRNA and the NPY‐Y1 receptor mRNA were elevated by running and the combined treatment. Moreover, correlations were detected between NPY mRNA levels and climbing and cell proliferation and NPY‐Y1 receptor mRNA levels and swimming. Our results suggest that increased cell proliferation is not necessarily associated with an antidepressant effect. However, treatments that were associated with an antidepressant‐like effect did regulate hippocampal levels of mRNAs encoding NPY and/or the NPY‐Y1 receptor and support the notion that NPY can stimulate cell proliferation and induce an antidepressant‐like response. © 2009 Wiley‐Liss, Inc.