Prior anatomical and functional studies have demonstrated the importance of the basolateral region of the amygdala in the regulation of anxiogenic and anxiolytic behaviors. In the present report we investigated the anxiety-inducing effects of the corticotropin-releasing hormone-related peptide urocortin 1 (Ucn1) and the gut-brain peptide ghrelin. Both peptides were injected directly into the basolateral amygdala of male Sprague-Dawley rats and performance in the elevated plus maze was assessed. Ghrelin was administered at doses of 3-300 pmol and Ucn1 at doses of 0.01-1.0 pmol. Separate groups of rats were pretreated with Ucn1 before ghrelin treatment. In all experiments each test was performed as a single trial per animal. Results indicated that both ghrelin and Ucn1 elicited an increase in anxiogenic behavior. Moreover, Ucn1 pretreament potentiated the anxiogenic action of ghrelin. Overall these findings provide support for an integrated role of ghrelin and urocortin signaling within the basolateral amygdala in the expression of anxiogenesis.

Prior research suggests that midbrain serotonergic signaling and hypothalamic ghrelinergic signaling both play critical roles in appetitive and emotional behaviors. In the present study, we investigated the effects of median raphe nucleus (MRN) somatodentritic 5-HT1A receptor activation on the feeding-stimulant and anxiogenic action of paraventricular nucleus (PVN) ghrelin. In an initial experiment, adult male Sprague-Dawley rats were injected with either ghrelin (200-800 pmol) into the PVN or 8-OH-DPAT (2.5-10 nmol), a 5-HT1A receptor agonist, into the MRN. Performance on the elevated plus maze (EPM) was then assessed. In separate rats, MRN 8-OH-DPAT (2.5-5 nmol) was administered 5 min prior to PVN injection of ghrelin (400 pmol) followed by EPM testing. The orexigenic effects of MRN 8-OH-DPAT (0.1-1.6 nmol) paired with PVN ghrelin (50 pmol) were also examined. When administered alone into the PVN, ghrelin significantly decreased the number of entries and time spent in the open arms of the EPM. This anxiogenic effect was blocked if rats were allowed to eat immediately after ghrelin administration and then tested in the plus maze. MRN injections of 8-OH-DPAT were anxiolytic, and when rats were pretreated with 8-OH-DPAT prior to ghrelin, the anxiogenic action of the peptide was attenuated. In contrast, MRN administration of 8-OH-DPAT potentiated the eating-stimulant effect of PVN ghrelin. Overall, our findings demonstrate that ghrelinergic and serotonergic circuits interact in the neural control of eating and anxiety-like behaviors, with 5-HT1A receptor mechanisms potentiating the orexigenic action of ghrelin while inhibiting ghrelin-induced anxiogenesis as measured via the EPM.

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