Nargol Ahmadi-Mahmoodabadi - Institute for Cognitive Science Studies, Tehran, Iran
Masoumeh Emamghoreishi - Department of Pharmacology, School of Medicine and Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
Mohammad Nasehi - Cognitive and Neuroscience Research Center, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
Mohammad-Reza Zarrindast - Institute for Cognitive Science Studies, Tehran, Iran

Objective(s): This study aimed at investigating the effect of serotonergic ۵-HT۴ receptor agonist/antagonist on memory consolidation deficit induced by ACPA (a potent, selective CB۱ cannabinoid receptor agonist) in the pre-limbic (PL) cortex. Materials and Methods: We used the step-through passive avoidance test to evaluate memory consolidation of male Sprague-Dawley (SD) rats. Bilateral post-training microinjections of the drugs were done in a volume of ۰.۶ μl/rat into the PL area (۰.۳ μl per side).Results: The results showed a significant interaction between RS۶۷۳۳۳ hydrochloride (۵-HT۴ receptor agonist) or RS۲۳۵۹۷-۱۹۰ hydrochloride (۵-HT۴ receptor antagonist) and ACPA on consolidation of aversive memory. RS۶۷۳۳۳ hydrochloride (۰.۵ μg/rat) enhanced consolidation of memory and its co-administration at the ineffective dose of ۰.۰۰۵ μg/rat with ineffective (۰.۰۰۱ μg/rat) or effective (۰.۱ μg/rat) doses of ACPA improved and prevented impairment of memory caused by ACPA, respectively. In other words, RS۶۷۳۳۳ had a bidirectional effect on ACPA-caused amnesia. While RS۲۳۵۹۷-۱۹۰ hydrochloride had no effect on memory at the doses used (۰.۰۰۵, ۰.۰۱, ۰.۱, or ۰.۵ μg/rat); but its concomitant use with an effective dose of ACPA (۰.۱ μg/rat) potentiated amnesia. None of the drugs had an effect on locomotor activity.Conclusion: This study revealed that activation or deactivation of the ۵-HT۴ receptors in the PL may mediate the IA memory impairment induced by ACPA indicating a modulatory role for the ۵-HT۴ serotonergic receptors.

ACPA, Pre-limbic cortex, Passive avoidance memory, RS۲۳۵۹۷-۱۹۰, RS۶۷۳۳۳