Abstract :
Introduction: The plethora of studies indicated that there is a cross talk relationship between
harmaline and serotonergic (5-HT) system on cognitive and non-cognitive behaviors. Thus,
the purpose of this study is to assess the effects of hippocampal 5-HT4 receptor on memory
acquisition deficit induced by harmaline. Methods: Harmaline was injected peritoneally, while 5-HT4 receptor agonist (RS67333) and
antagonist (RS23597-190) were injected intra-hippocampal. A single-trial step-down passive
avoidance, open field and tail flick tasks were used for measurement of memory, locomotor
activity and pain responses, respectively. Results: The data revealed that pre-training injection of higher dose of harmaline (1 mg/kg),
RS67333 (0.5 ng/mouse) and RS23597-190 (0.5 ng/mouse) decreased memory acquisition
process in the adult mice. Moreover, concurrent pre-training administration of subthreshold dose
of RS67333 (0.005 ng/mouse) or RS23597-190 (0.005 ng/mouse) with subthreshold dose of
harmaline (0.5 mg/kg, i.p.) intensify impairment of memory acquisition. All above interventions
did not change locomotion and tail flick behaviors. Discussion: The results demonstrated that the synergistic effect between both hippocampal
5-HT4 receptor agonist and antagonist with impairment of memory acquisition induced by
harmaline, indicating a modulatory effect for hippocampal 5HT4 receptor on Harmaline induced
amnesia.
