The drug-associated conditioned stimulus (CSs) come to influence drug-seeking and relapse behaviour through the memories they evoke.The animals undergo extinction training (no drug) will decrease response rates and extinction entails new learning rather than forgetting.In the model of conditioned place aversion (CPA) of acute morphine-dependent rats, we found that lesions of ventral medial prefrontal cortex (vmPFC) impaired the consolidation of extinction of CPA.In addition, we found that both extraeellular signal-regulated kinases (ERK) pathway and histone acetylation in vmPFC are involved in consolidation of extinction and also found that Trichostatin A, a histone deacetylase (HDAC) inhibitor, can facilitate the extinction of CPA.We further found that manipulation of vmPFC ERK activity by its antagonist U0126 and agonist D-cycloserine not only differentially influenced the behavior of CPA rats but also altered histone acetylation.Furthermore, we found that extinction of CPA increased BDNF exon Ⅰ but not exon Ⅳ in the vmPFC, We further found that the inereasement is accompanied by a significant increase in histone H3 acetylation and pCREB around the BDNF exon Ⅰ gene promoter.We also found that inhibition of trk B by intra-vmPFC injections of K252a significantly disrupted the consolidation of extinction.Therefore, our findings suggest that histone acetylation is mediated by ERK pathway and the increasement of BDNF protein expression in vmPFC are required for the consolidation of CPA extinction and the tyrosine kinase inhibitor K252a prevented the consolidation of CPA.