Abstract
Major depressive disorder (MDD) is arguably the largest contributor to the global disease and disability burden, but very few treatment options exist for juvenile MDD patients. Ghrelin is the principal hunger-stimulating peptide, and it has also been shown to reduce depressive-like symptoms in adult rodents. We examined the effects of intracerebroventricular (icv) injection of ghrelin on depressive-like behavior. Moreover, we determined whether ghrelin increased neurogenesis in the hippocampus. Ghrelin (0.2-nM, 0.5-nM, and 1.0-nM) was administered acutely by icv injection to juvenile rats to determine the most effective dose (0.5-nM) by a validated feeding behavior test and using the forced swim test (FST) as an indicator of depressive-like behavior. 0.5-nM ghrelin was then administered icv against an artificial cerebrospinal fluid (aCSF) vehicle control to determine behavioral changes in the tail suspension test (TST) as an indicator of depressive-like behavior. Neurogenesis was investigated using a mitogenic paradigm, as well as a neurogenic paradigm to assess whether ghrelin altered neurogenesis. Newborn hippocampal cells were marked using 5′-bromo-2′-deoxyuridine (BrdU) administered intraperitoneally (ip) at either the end or the beginning of the experiment for the mitogenic and neurogenic paradigms, respectively. We found that ghrelin administration increased immobility time in the TST. Treatment with ghrelin did not change mitogenesis or neurogenesis. These results suggest that ghrelin administration does not have an antidepressant effect in juvenile rats. In contrast to adult rodents, ghrelin increases depressive-like behavior in male juvenile rats. These results highlight the need to better delineate differences in the neuropharmacology of depressive-like behavior between juvenile and adult rodents.
Highlights
Juveniles with depression manifest a different array of symptoms than adults, which is one significant reason that major depressive disorder (MDD) may be underdiagnosed in juveniles (Yorbik et al, 2004)
All care and procedures involving rats were approved by the Kirksville College of Osteopathic Medicine (KCOM) Institution Animal Care and Use Committee (IACUC)
Showing that fluoxetine produced a measurable effect validated that the TST can be used to assess depressive-like behavior in juvenile rats
Summary
Juveniles with depression manifest a different array of symptoms than adults, which is one significant reason that major depressive disorder (MDD) may be underdiagnosed in juveniles (Yorbik et al, 2004). Ghrelin is a peptide hormone that has been found to have an acute antidepressant effect in adult rodents (Carlini et al, 2012), which is correlated with an increase of hippocampal neurogenesis (Moon et al, 2009). Some weak antidepressive effects of ghrelin in male depressed patients were reported (Kluge et al, 2011). Neurogenesis is required for some of the antidepressant effects of antidepressant drugs such as imipramine and fluoxetine (Santarelli et al, 2003). An increase in the rate of hippocampal neurogenesis was observed in human progenitor cells treated with antidepressant drugs (Belmaker and Agam, 2008; Anacker et al, 2011)
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