In a rat study, injecting a ghrelin‑like peptide (ghrp‑2) straight into the hippocampus boosted the animals' ability to learn a simple avoidance task, but it also made them more anxious. The effect was seen both in normal rats and in those without ovaries. The authors suggest that ghrelin’s action in the brain can both improve learning and trigger anxiety‑like behavior.

Hippocampus, amygdala and dorsal raphe nucleus are the cerebral main structures involved in learning, memory and anxiety. Ghrelin increases the level of several hormones in these structures and affects learning, memory and anxiety-like behaviors. This study was performed to investigate the effect of ghrelin agonist on passive avoidance learning and anxiety in adult female rats in the presence and absence of ovary hormones. Five groups of rats, including control group with no injections, ovariectomized groups; one group receiving normal saline and other group receiving ghrelin agonist solution, surgery shocked (sham operated) groups; one group receiving saline and other group ghrelin agonist solution, were tested. Inside stereotaxis apparatus, two sided CA1 cannulae were used and 1 microL of saline or ghrelin agonist solution, at 3 nmol microL(-1) concentration, was injected into each cannula. Passive avoidance learning was measured by using shuttle box and anxiety by elevated plus- maze. Ghrelin agonist increased the level of learning in surgery shocked group in comparison with control group. Anxiety-like behavior was seen in both ovariectomized and surgery shocked groups. Ghrelin agonist binds its own receptors in the hippocampus, thereby increases learning capability and induces anxiety-like behaviors. Proper management of these behaviors might be useful in controlling some forms of nervous system diseases in humans.