Endogenous opioid peptides contribute to associative LTP in the hippocampal CA3 region

► Induction of LTP at lateral (LPP) and medial (MPP) perforant path-CA3 synapses involves opioid and NMDA receptors, respectively. ► Associative PP-CA3 LTP is seen with intense coactivation of the alternate perforant pathway. ► Opioid receptor antagonists block associative MPP-CA3 LTP induced by coactivation of the LPP. ► NMDAR antagonists block associative LPP-CA3 LTP induced by intense coactivation of the MPP. ► Opioid peptides contained in opioidergic afferents contribute to the associative induction of NMDAR-dependent LTP.