Blocking the ghrelin receptor type 1a in the rat brain impairs memory encoding

•Ghrelin signaling in the brain is involved in cognitive processes.•Blocking ghrelin receptor type 1a impaired memory acquisition and consolidation.•Endogenous ghrelin is crucial for memory encoding in rats.

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 230–280 g 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 80 nM/5 μl; i.c.v) 10 min before, or (2, 20 and 80 nM/5 μl; 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.