Inhibition of hippocampal β-adrenergic receptors blocks the extinction-enhancing effect of novelty (Nov). a, d, Propranolol (Pro) at doses of 0, 0.3, and 1.0 μg was micro-infused into the CA1 area of the dorsal hippocampus before OF exposure. The OF was presented 1 h before or after extinction (Ext). Extinction LTM and reinstatement were then tested (n = 9–10 per group). b, e, Pretreatment with 1.0 μg propranolol prevented the enhancement of extinction LTM induced by novelty exploration 1 h before or after extinction. c, f, The decrease in freezing time in the reinstatement test induced by OF exploration was also blocked by propranolol. g, Time line and representative Western blots. Saline or propranolol (1.0 μg) was micro-infused into the CA1 before OF exposure. The rats were decapitated 30 min after OF exploration (n = 6 per group). h, Propranolol prevented the increase in phosphorylated PKA (pPKA) and phosphorylated CREB (pCREB) induced by novelty. Data are expressed as mean ± SEM; *p < 0.05. i, Schematic representation and photomicrographs of cannula placements in the CA1 area of the dorsal hippocampus. CFC, contextual fear conditioning tCREB, total CREB; tPKA, total PKA.