Studies have shown that intracerebral administration of ghrelin hormone affects learning and memory in different experimental models of learning. However, the effect of antagonism of ghrelin receptor type 1a (GHS-R1a) on different stages of learning has not been investigated. In this study the effect of intracerebroventricular (i.c.v) injection of a GHS-R1a selective antagonist (d-Lys-3-GHRP-6) was examined on acquisition and consolidation of learning in the passive avoidance task. In total, 72 male Wistar rats weighing 230-280g were randomly distributed into 9 groups of 8 each. Animals underwent stereotaxic surgery and cannulated in their right ventricle. One week after surgery, the rats received different doses of d-Lys-3-GHRP-6 (0.2, 2, 20 and 80nM/5μl; i.c.v) 10min before, or (2, 20 and 80nM/5μl; i.c.v) immediately after training. The control groups received solvent of the drug. Twenty four hours later in the test day, memory retrieval was assessed. Pre-training injection of d-Lys-3-GHRP-6 decreased step-through latency (STL) and increased number of step-throughs into the dark compartment (NST) in a dose-dependent manner, but failed to be statistically significant. It also increased time spent in the dark compartment (TDC), significantly and in a dose-dependent manner. Post-training injection of d-Lys-3-GHRP-6 decreased step-through latency and increased time spent in the dark compartment and number of step-throughs into the dark compartment, significantly and in a dose-dependent manner. The results indicate that antagonism of the GHS-R1a in the rat brain impairs memory encoding on both acquisition and consolidation stages. Further studies are required to elucidate the main brain regions affected by the antagonist. Copyright © 2015 Elsevier B.V. All rights reserved.
Siamak Beheshti, Shahrzad Shahrokhi. Blocking the ghrelin receptor type 1a in the rat brain impairs memory encoding. Neuropeptides. 2015 Aug;52:97-102
PMID: 26072187
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