Discriminating between overlapping experiences is essential for effective retrieval of episodic memories. In rodents, this process can be examined with the Object-in-Context (OIC) task, where contextual cues guide the selection between competing memories. The prefrontal cortex (PFC) plays a pivotal role in this selection, and serotonergic signaling—particularly through 5-HT2A receptors—has been implicated in controlling memory interference. Pharmacological blockade of 5-HT2A receptors in the PFC impairs interference resolution without affecting attentional processes. The hippocampus (HIP), via its projections to the PFC, may convey contextual information and modulate mPFC activity through theta oscillations. Local field potential (LFP) recordings revealed enhanced theta power in the ventral HIP and PFC during object exploration, with increased HIP–PFC coherence when animals explored incongruent objects, correlating with behavioral performance. To assess the impact of 5-HT2A receptor blockade on HIP–PFC communication, Wistar rats were implanted with tetrodes and cannulas in the PFC and electrodes in the HIP. Preliminary data indicate that local 5-HT2A antagonist infusion in PFC decreases HIP–PFC coherence during incongruent object exploration, suggesting a possible link to the animals’ impaired task performance.