Acute nicotine disrupts consolidation of contextual fear extinction and alters long-term memory-associated hippocampal kinase activity

- Acute nicotine within the consolidation window impaired fear extinction.
- Acute nicotine outside the consolidation window did not affect fear extinction.
- vHPC pJNK1 and pERK1/2 were downregulated by pre-extinction acute nicotine.
- Post-extinction acute nicotine upregulated vHPC pERK1/2.

Previous research has shown that acute nicotine, an agonist of nAChRs, impaired fear extinction. However, the effects of acute nicotine on consolidation of contextual fear extinction memories and associated cell signaling cascades are unknown. Therefore, we examined the effects of acute nicotine injections before (pre-extinction) and after (post-extinction) contextual fear extinction on behavior and the phosphorylation of dorsal and ventral hippocampal ERK1/2 and JNK1 and protein levels on the 1st and 3rd day of extinction. Our results showed that acute nicotine administered prior to extinction sessions downregulated the phosphorylated forms of ERK1/2 in the ventral hippocampus, but not dorsal hippocampus, and JNK1 in both dorsal and ventral hippocampus on the 3rd extinction day. These effects were absent on the 1st day of extinction. We also showed that acute nicotine administered immediately and 30 min, but not 6 h, following extinction impaired contextual fear extinction suggesting that acute nicotine disrupts consolidation of contextual fear extinction memories. Finally, acute nicotine injections immediately after extinction sessions upregulated the phosphorylated forms of ERK1/2 in the ventral hippocampus, but did not affect JNK1. These results show that acute nicotine impairs contextual fear extinction potentially by altering molecular processes responsible for the consolidation of extinction memories.