D-Lys-3-GHRP-6 impairs memory consolidation and downregulates the hippocampal serotonin HT1A, HT7 receptors and glutamate GluA1 subunit of AMPA receptors

Abstract

Antagonism of the functional ghrelin receptors impairs memory formation, but the underlying mechanisms are not well-known. We aimed to evaluate the effect of intracerebral injection of a ghrelin receptor antagonist (D-Lys-3-GHRP-6) on memory consolidation in the inhibitory avoidance task and on the gene expression levels of serotonin HT1A and HT7 receptors, glutamate GluN1 subunit of the NMDA and GluA1 subunit of the AMPA receptors and calcium/calmodulin kinase II-α in the hippocampus of rats. Thirty adult male rats were implanted with cannulas in their lateral ventricles. Three groups of animals (n=5) received D-Lys-3-GHRP-6 (0.5 and 5nM) or saline immediately post-training. Twenty-four hours later, memory retrieval was assessed. Three additional groups of animals (n=5) received D-Lys-3-GHRP-6 (0.5 and 5nM) or saline, but animals in these groups were decapitated, and their hippocampus was removed, 24 hours thereafter. The target gene expression levels were measured using a quantitative real-time PCR method. D-Lys-3-GHRP-6 impaired memory consolidation. Meanwhile, it led to a significant downregulation of the mRNA expression levels of the hippocampal serotonin HT1A and HT7 receptors and glutamate GluA1 subunit of the AMPA receptors, but could not affect that of GluN1 subunit of the NMDA receptors and CaMKII-α. It seems that part of the impairing effect of D-Lys-3-GHRP-6 on inhibitory avoidance memory consolidation might be due to a decrease in the expression of serotonin HT1A and HT7 receptors and glutamate AMPA receptors in the hippocampus of rats.