Objective(s): This study aimed at investigating the effect of serotonergic 5-HT4 receptor agonist/ antagonist on memory consolidation deficit induced by acpa (a potent, selective CB1 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 0. 6 μ l/rat into the PL area (0. 3 μ l per side). Results: The results showed a significant interaction between RS67333 hydrochloride (5-HT4 receptor agonist) or RS23597-190 hydrochloride (5-HT4 receptor antagonist) and acpa on consolidation of aversive memory. RS67333 hydrochloride (0. 5 μ g/rat) enhanced consolidation of memory and its coadministration at the ineffective dose of 0. 005 μ g/rat with ineffective (0. 001 μ g/rat) or effective (0. 1 μ g/rat) doses of acpa improved and prevented impairment of memory caused by acpa, respectively. In other words, RS67333 had a bidirectional effect on acpa-caused amnesia. While RS23597-190 hydrochloride had no effect on memory at the doses used (0. 005, 0. 01, 0. 1, or 0. 5 μ g/rat); but its concomitant use with an effective dose of acpa (0. 1 μ g/rat) potentiated amnesia. None of the drugs had an effect on locomotor activity. Conclusion: This study revealed that activation or deactivation of the 5-HT4 receptors in the PL may mediate the IA memory impairment induced by acpa indicating a modulatory role for the 5-HT4 serotonergic receptors.