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.
Yamazaki
Yoshihiko
Y
Department of Neurobiology and Behavior, University of California Irvine, CA 92697-4550, USA.
Jia
Yousheng
Y
Niu
Rong
R
Sumikawa
Katumi
K
D000818:Animals; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D017774:Long-Term Potentiation; D036881:Long-Term Synaptic Depression; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D018091:Receptors, AMPA / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism
C121001:NR2B NMDA receptor; D018722:Nicotinic Agonists; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D014443:Tyrosine; D009538:Nicotine; D011505:Protein-Tyrosine Kinases