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Vasoactive intestinal peptide (VIP), an important modulator of hippocampal synaptic transmission, influences exploration and hippocampal‐dependent learning in rodents. Homosynaptic long‐term depression (LTD) and depotentiation are two plasticity phenomena implicated in learning of behavior flexibility and spatial novelty detection. In this study, we investigated the influence of endogenous VIP on LTD and depotentiation induced by low‐frequency stimulation (1 Hz, 900 pulses) of the hippocampal CA1 area in vitro in juvenile and young adult rats, respectively. LTD and depotentiation were enhanced by the VIP receptor antagonist Ac‐Tyr¹, D‐Phe² GRF (1–29), and the selective VPAC₁ receptor antagonist, PG 97–269, but not the selective VPAC₂ receptor antagonist, PG 99–465. This action was mimicked by an anti‐VIP antibody, suggesting that VIP, and not pituitary adenylate cyclase‐activating polypeptide …