The hypothalamic arcuate nucleus (
Arc) is the presumed target site for the orexigenic
hormone ghrelin, which is secreted from the stomach during fasting.
Ghrelin directly activates
Arc neurones. Similar to exogenous
ghrelin, overnight food deprivation also induces c-Fos expression in the
Arc of mice. In the present study, we tested the role of endogenous
ghrelin in the fasting-induced c-Fos expression in the
Arc of mice. We used
NOX-B11-3, the latest generation of the recently developed
ghrelin-binding compounds, so-called
RNA Spiegelmers (SPM) to block endogenous
ghrelin action during food deprivation. The specificity and potency of this compound was also tested in electrophysiological and immunohistological experiments. In electrophysiological in vitro single cell recordings,
NOX-B11-3 effectively blocked the excitatory effect of
ghrelin in the medial
Arc (ArcM) of rats whereas the biologically inactive control SPM had no effect. Furthermore,
NOX-B11-3 (15 mg/kg i.p.) potently suppressed
ghrelin-induced (25 microg/kg s.c., 12 h after SPM injection) c-Fos expression in the
Arc. However, when injected at the beginning of a 14-h fasting period, the same dose of
NOX-B11-3 had no effect on the c-Fos expression in the
Arc of mice. These results demonstrate that
NOX-B11-3 is a long-acting compound, which effectively blocks the effect of exogenous
ghrelin on neuronal activity in the
Arc under in vitro and in vivo conditions. Furthermore, increased
ghrelin signalling does not appear to be a necessary factor for the activation of
Arc neurones during food deprivation or other fasting-related signals might have masked or compensated for the loss of the
ghrelin effect.