Hippocampal NOP Receptor Activation Impairs Object Recognition Memory Acquisition

Nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the NOP receptor, modulates learning and memory, yet its precise hippocampal function remains unclear. Here, we examined how activation of hippocampal NOP receptors influences distinct stages of object recognition memory (ORM) processing. Adult male Wistar rats trained in the novel object recognition task received bilateral intra-dorsal CA1 infusions of N/OFQ either 20 min before or 5 min after training, or 20 min before a 1-day retention test. Pre-training N/OFQ infusion markedly impaired ORM retention without affecting locomotor or exploratory behavior, whereas post-training or pre-test infusions had no effect, even at more than threefold higher. The selective NOP receptor antagonist UFP-101 completely blocked the amnesic effect of N/OFQ but had no influence alone. Pre-training N/OFQ administration also failed to alter performance in the step-down inhibitory avoidance task, excluding sensory or motivational confounds. Thus, hippocampal NOP receptor activation selectively disrupts ORM acquisition while sparing consolidation and recall, identifying the N/OFQ-NOP system as a negative modulator of hippocampal encoding mechanisms critical for recognition memory formation.