Nicotine exposure in vivo induces long-lasting enhancement of NMDA receptor-mediated currents in the hippocampus

The use of nicotine via cigarette smoking forms long‐lasting memories that are recalled in response to environmental cues associated with previous nicotine use. However, the changes in brain memory systems that underlie these long‐lasting memories are not well understood. The N‐methyl‐d‐aspartate receptor (NMDAR) is critical for long‐lasting modifications of synapses. Here we show that in vivo nicotine exposure induces the enhancement of NR2B‐containing NMDAR‐mediated currents in the hippocampus, a brain region associated with the formation of memories. This nicotine effect is maintained during continued nicotine exposure and is accompanied by increased tyrosine phosphorylation of NR2B. Furthermore, long‐term potentiation (LTP), which is considered to be a cellular substrate of learning and memory, induced in nicotine‐exposed hippocampi contains a protein synthesis‐independent long‐lasting component. An NR2B‐selective antagonist blocks a long‐lasting component of LTP, but not LTP. These results suggest that exposure to nicotine provides conditions that promote the induction of long‐lasting modifications of synapses, which may be involved in the formation of memories involving nicotine use.