The Role of Ghrelin Receptor Constitutive Activity in Fear Memory: Hippocampal Excitability, Long-Term Potentiation, and Behavioral Implications Publisher Pubmed



Beheshti S ; Halabian A ; Razavizadeh FS ; Radahmadi M ; Badiyifard A
Source: Physiology and Behavior Published:2026

Abstract

Various studies have validated the impact of ghrelin on different stages of memory formation. We evaluated the effect of blocking the constitutive activity of the ghrelin functional receptor (GHS-R1a) in the rat amygdala by injecting a GHS-R1a inverse agonist, [D-Arg, D-Phe, D-Trp, Leu] substance P (D-SP)] on the consolidation and retrieval of passive avoidance memory. Meanwhile, the effect of intra CA1 injection of D-SP was assessed on the induction of long-term potentiation (LTP) in the hippocampus. Two guide cannulas were placed in the right and left basolateral nuclei of the amygdala, stereotaxically. Animals received D-SP (50 and 500 ng/rat) or saline in the amygdala at post-training, or pre-test stages to investigate memory performance. Two other groups of animals received D-SP (500 ng/rat) or saline in the hippocampal CA1 area. An intact group without any injections was also included. The input/output (I/O) functions and the induction of LTP were measured. The results showed that post-training injection of D-SP significantly reduced step-through latency and increased the duration of staying in the dark room. The pre-test injection of D-SP significantly reduced step-through latency and increased the number of entries into the dark room. D-SP significantly decreased the slope and amplitude of the I/O fEPSP. Moreover, the slope and amplitude of fEPSP were reduced significantly in these groups following the induction of LTP. The results show a positive role of the constitutive activity of GHS-R1a in the amygdala for the consolidation and probably retrieval of memory and for LTP induction in the hippocampus. © 2026 Elsevier Inc.