The Ghrelin/GHS-R1a Pathway is Involved in the Mechanism of the CTA-regulated Neuronal Loop

The Ghrelin/GHS-R1a Pathway is Involved in the Mechanism of the CTA-regulated Neuronal Loop

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Author(s): Qian Wang

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DOI: 10.18483/ijSci.1182 268 625 64-72 Volume 6 - Jan 2017


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).


Ghrelin, insular cortex, CNO, CTA, GI-DREADD System


  1. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402:656-660.
  2. Gao Q, Horvath TL (2008) Neuronal control of energy homeostasis. FEBS Lett 582:132-141.
  3. Yang J, Brown MS, Liang G, Grishin NV, Goldstein JL (2008) Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone. Cell 132:387-396.
  4. Andrews ZB (2011) The extra-hypothalamic actions of ghrelin on neuronal function. Trends Neurosci 34:31-40.
  5. Wittekind, D.A. and M. Kluge, Ghrelin in psychiatric disorders - A review. Psychoneuroendocrinology. 2015 Feb;52:176-94.
  6. Wellman, M. and A. Abizaid, Growth Hormone Secretagogue Receptor Dimers: A New Pharmacological Target(1,2,3). eNeuro. 2015 Apr 24;2(2).
  7. Steiger, A., et al., Ghrelin in mental health, sleep, memory. Mol Cell Endocrinol, 2011.340(1): p. 88-96.
  8. Yoshitake Sano, Justin L. Shobe, Miou Zhou,Shan Huang,et al.CREB Regulates Memory Allocationin the Insular Cortex.Current Biology 24, 2833–2837, December 1, 2014
  9. Duncan A. A. MacLaren, Richard W. Clozapine N-Oxide Administration Produces Behavioral Effects in Long–Evans Rats:Implications for Designing DREADD Experiments.ENEURO.0219-16.2016
  10. Jeongsoo Hana,, Myeounghoon Cha, Minjee Kwona,, Seong-Karp Hongc, Sun Joon Baid.In vivo voltage-sensitive dye imaging of the insular cortex in nerve-injured rats.Neuroscience Letters 634 (2016) 146–152
  11. Timothy A. Allen , Nandakumar S.Imaging the spread of reversible brain inactivations using fluorescent muscimol.Journal of Neuroscience Methods 171 (2008) 30–38.
  12. Song L, Zhu Q, Liu T, Yu M, Xiao K, Kong Q, Zhao R, Li GD, Zhou Y (2013) Ghrelin modulates lateral amygdala neuronal firing and blocks acquisition for conditioned taste aversion. PLoS One 8:e65422.
  13. Zhu Q, Xiao K, Yu M, Niu M, Li C, Gao Y, Li GD, Zhou Y (2013) Ghrelin but not nesfatin-1 affects certain forms of learning and memory in both rats and mice. Brain Res 1541:42-51.
  14. Blaine N. Armbruster, Xiang Li,et al.Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand.Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5163-8. Epub 2007 Mar 2.

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International Journal of Sciences is Open Access Journal.
This article is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License.
Author(s) retain the copyrights of this article, though, publication rights are with Alkhaer Publications.

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