Beyond appetite: Acylated ghrelin as a learning, memory and fear behavior-modulating hormone

• Published in: Neuroscience and biobehavioral reviews 2022-12, Vol.143, p.104952, Article 104952
• Main Authors: Reich, Niklas, Hölscher, Christian
• Format: Article
• Language: English
• Subjects: Acylated ghrelin; Alzheimer’s disease; Amygdala - physiology; Appetite; Chronic stress; Conditioned taste aversion; Dopamine; Fear - physiology; Fear memory; Food reward response; Ghrelin - metabolism; Hippocampus - physiology; Humans; Memory - physiology; Neurogenesis; Post-traumatic stress disorder; Serotonin; Synaptic plasticity
• ISSN: 0149-7634; 1873-7528
• DOI: 10.1016/j.neubiorev.2022.104952

Although often referred to as a hunger hormone, recent evidence highlights a neuroprotective function of acylated ghrelin (AG) and a substantial role in the regulation of declarative and aversive memories as well as fear behavior. As such, in this review, we i) evaluate what specific stages and forms of memory, as well as which respective brain areas are affected by acylated ghrelin, ii) illustrate the plasticity-associated signaling pathways of AG in the hippocampus, also involving memory resolution-enhancing neurogenesis, iii) elucidate how the peptide modulates neurotransmitter systems (glutamate, γ-aminobutyric acid, dopamine, serotonin), iV) clarify the role of AG in conditioned taste aversion, novelty learning and the formation of spatial, recognition, auditory fear, contextual fear and passive avoidance memories in the hippocampus and amygdala as well as V) solve the mystery behind AG, its impact on the 5-HT system, the recently established link to post-traumatic stress disorder and the either fear-suppressing or fear-potentiating effects under neutral and acutely stressed conditions or chronic stress, respectively. •Ghrelin enhances glutamatergic neurotransmission and declarative memory.•Ghrelin-induced neurogenesis improves hippocampal pattern separation.•Ghrelin discourages conditioned taste aversion to support feeding behaviour.•Ghrelin enhances passive avoidance and blocks cued fear memory consolidation.•During chronic stress, ghrelin exacerbates post-traumatic stress disorder and fear.