In a study, ghrellin was elevated in mice (either through caloric restriction or subcutaneous injections) showed less depressive like symptoms in forced swim test. On the chronic social defeat stress scale, ghr-KO mice showed more social avoidance than wild-type after periods of struggle with a dominant animal. Systemic treatment with a neuroprotective compount enhanced neurogenesis in the hippocampus leading to antidepressant effects - it was speculated that ghrelin’s antidepressant properties are mediated by neurogenic properties. The same effects were seen after administration in mice that had undergone olfactory bulbectomy, same with group with reduced AVP gene expression. Ghrelin also increases noradrenergic and serotonergic transmission. Two studies suggested contrasting results - increased long term ghrelin caused depressogenic properties through decreased serotonergic transmission in the dorsal raphe nuclei and pro depression effects; and then injecting anti-sense strand into the lateral ventricle induced anti-depressant effects(but authors did not measure ghrelin level to give a clearer indication that the observed effects are related to ghrelin system).
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