Ghrelin modulates lateral amygdala neuronal firing and blocks acquisition for conditioned taste aversion

PLoS One. 2013 Jun 7;8(6):e65422. doi: 10.1371/journal.pone.0065422. Print 2013.

Abstract

Ghrelin is an orexigenic brain-gut hormone promoting feeding and regulating energy metabolism in human and rodents. An increasing number of studies have reported that ghrelin and its identified receptor, the growth hormone secretagogue receptor 1a (GHS-R1a), produces remarkably wide and complex functions and biological effects on specific populations of neurons in central nervous system. In this study, we sought to explore the in vivo effects of acute ghrelin exposure on lateral amygdala (LA) neurons at the physiological and behavioral levels. In vivo extracellular single-unit recordings showed that ghrelin with the concentration of several nanomolars (nM) stimulated spontaneous firing of the LA neurons, an effect that was dose-dependent and could be blocked by co-application of a GHS-R1a antagonist D-Lys3-GHRP-6. We also found that D-Lys3-GHRP-6 inhibited spontaneous firing of the LA neurons in a dose-dependent manner, revealing that tonic GHS-R1a activity contributes to orchestrate the basal activity of the LA neurons. Behaviorally, we found that microinfusion of ghrelin (12 ng) into LA before training interfered with the acquisition of conditioned taste aversion (CTA) as tested at 24 h after conditioning. Pre-treatment with either purified IgG against GHS-R1a or GHS-R1a antagonist blocked ghrelin's effect on CTA memory acquisition. Ghrelin (12 ng) had no effect on CTA memory consolidation or the expression of acquired CTA memory; neither did it affect the total liquid consumption of tested rats. Altogether, our data indicated that ghrelin locally infused into LA blocks acquisition of CTA and its modulation effects on neuronal firing may be involved in this process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Action Potentials / drug effects*
  • Amygdala / cytology*
  • Animals
  • Cell Count
  • Conditioning, Psychological / drug effects*
  • Ghrelin / pharmacology*
  • Humans
  • Immunoglobulin G / administration & dosage
  • Immunoglobulin G / pharmacology
  • In Vitro Techniques
  • Male
  • Memory / drug effects
  • Neurons / drug effects
  • Neurons / physiology*
  • Oligopeptides / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Ghrelin / antagonists & inhibitors
  • Receptors, Ghrelin / metabolism
  • Taste / drug effects*

Substances

  • GHRP-6, Lys(3)-
  • Ghrelin
  • Immunoglobulin G
  • Oligopeptides
  • Receptors, Ghrelin
  • 6-Cyano-7-nitroquinoxaline-2,3-dione

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (31171079, 81070881 and 31222027 to YZ) and the Provincial Natural Science Foundation of Shandong (JQ201209 to YZ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.