Acute ghrelin effects on depressive-like behavior in bulbectomyced mice: a possible mechanism of action.

CARLINI VP ; MARTINI AC; KUMAR P; SAWANT R; RASK-ANDERSEN M; FREDRIKSSON R; RUBIALES DE BARIOGLIO S; SCHIÖTH HB; FIOL DE CUNEO M

Florencia

Congreso; 15th International and 14th European Congress of Endocrinology; 2012

Ghrelin (Ghr) is an orexigenic peptide investigated by Lutter and col. 2008 for its potential role in the development of depressive symptoms induced by chronic stress, suggesting that Ghr defends against depressive-like symptoms. Rodent bilateral olfactory bulbectomy (OB) is an animal model that appears to fulfill many of the criteria required for the study of depression; hence, Ghr could be an alternative therapeutic tool for depression therapy. We study the possibility that Ghr could reverse some depressive-like behaviors induced by OB in mice, using the tail suspension test (TST), a test predictive of antidepressant activity, and Ghr effect on mood regulatory hormones. Adult female Albino’s Swiss mice were divided in sham and OB, and subsequently infused with intracerebroventricular (ICV) saline (S) or Ghr (0.03 or 3.0 nmol/µl). After the TST was applied, mice were sacrificed and the hypothalamus was dissected in order to study the mRNA expression of genes related to mood using real time PCR. The OB animals treated with S (OB-S) presented an increase on immobility time compared to sham (p<0.05), but the acute infuse of Ghr 3.0 nmol/µl induced a decrease on immobility time (p ≤0.05). The OB infused with Ghr 0.3 nmol/ul showed higher expression of delta opioid receptor (DOR) compared to OB-S (F=5.484, p=0.009) and sham that received the same dose of Ghr (F= 8.243, p = 0.0072). Similar effect was observed in the expression of kappa (p<0.05) and Mu (p<0.01) opioid receptor. The results show that Ghr 3.0 nmol/µl could reverts the immobility response in OB mice and provide information about the molecular mechanisms of this effect, showing its potential as antidepressant drug.