Abstract
Objective: We aimed to investigate the effects of ghrelin and its receptor GHS-R1a on the regulation of taste aversion-associated emotional memory. Methods: We studied the effect of selective and reversible inactivation of emotion-associated neurons on emotions processed by the local neuronal loop of the lateral amygdala and insular cortex. We used intraperitoneal clozapine-N oxide (CNO) injection, local brain microinjection, and taste aversion test. Results: Microinjection of ghrelin into the lateral amygdala blocked the acquisition of taste aversion memory in mice. However, microinjection of ghrelin did not affect memory consolidation. Adeno-associated virus (AAV) microinjection into the lateral amygdaloid nucleus blocked the acquisition of taste aversion memory in mice. Moreover, intraperitoneal injection of CNO inhibited taste aversion memory formation, altering the aversion index. Conclusion: Microinjection of ghrelin and AAV-CaMKII-hM4Di-2A-GHS-R1a-GFP into the lateral amygdala inhibited the acquisition of conditioned taste aversion in mice. The inhibition of the memory formation was achieved through the activation of growth hormone secretagogue receptor 1a (GHS-R1a).
Highlights
Ghrelin is a 28 amino acid protein
The physiological function of ghrelin is exerted through the activation of the ghrelin receptor[2,3]—growth hormone secretagogue receptor 1a (GHS-R1a)
Expression levels of GHS-R1a mRNA in the lateral amygdala were higher than in the central nucleus of the amygdala in mice. These results suggest that ghrelin/GHS-R1a and the corresponding downstream signaling pathways might regulate neuronal activity in the lateral amygdala
Summary
Ghrelin is a 28 amino acid protein. Ghrelin was first reported by Kojima et al in 1999 in mice, human gastric mucosa cells, and human hypothalamic arcuate nucleus. Ghrelin strongly promotes the secretion of growth hormone1. The physiological function of ghrelin is exerted through the activation of the ghrelin receptor[2,3]—growth hormone secretagogue receptor 1a (GHS-R1a). GHS-R1a is a G protein-coupled receptor comprised of seven transmembrane regions. Both ghrelin and GHS-R1a are involved in the regulation of memory, learning, motivation and reward, and anxiety and depression. Ghrelin and GHS-R1a are associated with the pathology of many neuropsychiatric diseases involving emotional and cognitive disorders, such as schizophrenia, depression, epilepsy, addiction, and neurodegeneration[4,5,6]
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