Vahideh Sahraiian - Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.
Homayoun Khazali - Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.

Background: Memory-dependent psychological behaviors have an important role in life. Memory strengthening in adulthood to prevent its defects in aging is a significant issue. The ghrelin endogenous hormone improves memory by targeting glutamatergic and serotonergic circuits. Also, citicoline, a memory strengthening drug in aging, is not recommended to adults due to its side effects. The current study aims to test that ghrelin treatment, like citicoline, would improve passive avoidance memory via expression of the genes encoding the N-methyl-D-aspartate receptor (NMDAR۱) and the serotonin receptor ۱A (HTR۱a) involved in this process. Methods: Five groups of adult male rats received (۱) saline (as control), (۲) ۰.۵ mg/kg citicoline, or (۳-۵) ۰.۳, ۱.۵, and ۳ nmol/μl ghrelin). The rats received the drugs via intra-hippocampal injection. Passive avoidance memory was determined using a shuttle box device. The latency to enter the dark chamber before (IL) and after (RL) injection and the total duration of the animal's presence in the light compartment (TLC) were evaluated. Then, the gene expression rates of NMDAR۱ and HTR۱a were measured by the Real-Time PCR.  Results: Ghrelin and citicoline had some similar and significant effects on passive avoidance memory, and both increased NMDAR۱ and decreased HTR۱a expression.  Conclusions: Ghrelin, like citicoline, improves passive avoidance learning by altering the NMDAR۱ and HTR۱a expression in the hippocampus.

Citicoline, Ghrelin, HTR۱a, Intrahippocampal injection, NMDAR۱, Passive Avoidance Memory.