Dopamine D3 receptors (D3Rs) regulate several brain functions such as reward and social behavior by modulating neuronal activity in different brain regions. Although mostly expressed in dopaminergic areas, D3Rs are also present in the hippocampus. Previous results obtained in our laboratory suggested that D3 pharmacological blockade or genetic deletion in D3-knock-out (KO) mice enhanced hippocampal long-term potentiation (LTP) and memory. Based on these findings, here, we aimed to explore the molecular bases underlying this pro-cognitive effect.To determine whether D3R blockade acted via pre- and/or post-synaptic mechanisms, we performed electrophysiological experiments at CA3-CA1 hippocampal synapses using field recordings and whole-cell patch-clamp techniques. Concurrently, we assessed protein expression performing western blot (WB) experiments on the same hippocampal slices used for LTP electrophysiological recordings. Additionally, we used electron microscopy (EM) to evaluate D3R distribution and sub-localization in CA1 glutamatergic neurons.We found that the selective D3R antagonist NGB-2904 enhanced basal synaptic transmission (BST) and AMPA current amplitude without affecting presynaptic forms of plasticity such as post-tetanic potentiation and paired-pulse facilitation.WB experiments revealed an increased expression of the post-synaptic proteins PSD, phospho(p)GluA1 and p-CREB in hippocampal slices from WT mice treated with NGB-2904 or from D3-KO mice. EM analysis of D3R distribution in CA1 glutamatergic neurons confirmed a higher D3R expression in the post-synaptic dendrites compared to axon terminals.In conclusion, our findings suggest that D3Rs predominantly influence hippocampal synaptic plasticity through post-synaptic mechanisms, consistent with their subcellular distribution.