Extinction is the learned inhibition of retrieval. Recently it was shown that a brief exposure to a novel environment enhances the extinction of contextual fear in rats, an effect explainable by a synaptic tagging-and-capture process. Here we examine whether this also happens with the extinction of another fear-motivated task, inhibitory avoidance (IA), and whether it depends on dopamine acting on D1 or D5 receptors. Rats were trained first in IA and then in extinction of this task. The retention of extinction was measured 24 h later. A 5-min exposure to a novel environment 30 min before extinction training enhanced its retention. Right after exposure to the novelty, animals were given bilateral intrahippocampal infusions of vehicle (VEH), of the protein synthesis inhibitor anisomycin, of the D1/D5 dopaminergic antagonist SCH23390, of the PKA inhibitor Rp-cAMP or of the PKC inhibitor Gö6976, and of the PKA stimulator Sp-cAMP or of the PKC stimulator PMA. The novelty increased hippocampal dopamine levels and facilitated the extinction, which was inhibited by intrahippocampal protein synthesis inhibitor anisomysin, D1/D5 dopaminerdic antagonist SCH23390, or PKA inhibitor Rp-cAMP and unaffected by PKC inhibitor Gö6976; additionally, the hippocampal infusion of PKA stimulator Sp-cAMP reverts the effect of D1/D5 dopaminergic antagonist SCH 23390, but the infusion of PKC stimulator PMA does not. The results attest to the generality of the novelty effect on fear extinction, suggest that it relies on synaptic tagging and capture, and show that it depends on hippocampal dopamine D1 but not D5 receptors.dopamine | inhibitory avoidance | modulation of extinction | novelty | behavioral tagging and capture F rey and Morris (1, 2) described the enhancing influence of neuronal plastic processes [long-term potentiation (LTP) or long-term depression (LTD)] generated at one set of hippocampal synapses on LTP and LTD generated at other synapses. This influence is explainable by interactions between new proteins, called plasticity-related proteins (PRPs), at the two sets of synapses; the PRPs that tag one of them can be captured by those of others and enhance their responsiveness (3-5). Many memories rely on hippocampal LTP and LTD (1, 2, 6-11), and the "synaptic tagging-and-capture" process has been applied to the explanation of interactions between concurrent memories (11-13), among which are novelty and fear acquisition (12,14) and novelty and fear extinction (15, 16). Exposure to novelty [an open field (OF) in which they had never been before] involves two consecutive processes: its detection, which is very brief (seconds), and the immediately ensuing habituation (17), which lasts much longer; both rely on hippocampal LTD (18). With a relatively restricted time window before and/or after an extinction trial, novelty can enhance the extinction of contextual fear conditioning (CFC) lastingly (15,16). This is obviously of potential importance for exposure therapy (18-21).In rodents, the exploration of a novel environment, object, ...