Nicotine shifts the temporal activation of hippocampal protein kinase A and extracellular signal-regulated kinase 1/2 to enhance long-term, but not short-term, hippocampus-dependent memory.
Acute nicotine enhances hippocampus-dependent learning through nicotine binding to β2-containing nicotinic acetylcholine receptors (nAChRs), but it is unclear if nicotine is targeting processes involved in short-term memory (STM) leading to a strong long-term memory (LTM) or directly targeting LTM. In addition, the molecular mechanisms involved in the effects of nicotine on learning are unknown. Previous research indicates that protein kinase A (PKA), extracellular signal-regulated kinase 1/2 (ERK1/2), and protein synthesis are crucial for LTM. Therefore, the present study examined the effects of nicotine on STM and LTM and the involvement of PKA, ERK1/2, and protein synthesis in the nicotine-induced enhancement of hippocampus-dependent contextual learning in C57BL/6J mice. The protein synthesis inhibitor anisomycin impaired contextual conditioning assessed at 4 h but not 2 h post-training, delineating time points for STM (2 h) and LTM (4 h and beyond). Nicotine enhanced contextual conditioning at 4, 8, and 24 h but not 2 h post-training, indicating nicotine specifically enhances LTM but not STM. Furthermore, nicotine did not rescue deficits in contextual conditioning produced by anisomycin, suggesting that the nicotine enhancement of contextual conditioning occurs through a protein synthesis-dependent mechanism. In addition, inhibition of dorsal hippocampal PKA activity blocked the effect of acute nicotine on learning, and nicotine shifted the timing of learning-related PKA and ERK1/2 activity in the dorsal and ventral hippocampus. Thus, the present results suggest that nicotine specifically enhances LTM through altering the timing of PKA and ERK1/2 signaling in the hippocampus, and suggests that the timing of PKA and ERK1/2 activity could contribute to the strength of memories.
Department of Psychology, Neuroscience Program, Temple University, Weiss Hall, 1701 N. 13th Street, Philadelphia, PA 19122, United States. Electronic address: tgould@temple.edu.
Thomas J
TJ
Gould
Department of Psychology, Neuroscience Program, Temple University, Weiss Hall, 1701 N. 13th Street, Philadelphia, PA 19122, United States.
Derek S
DS
Wilkinson
Department of Psychology, Neuroscience Program, Temple University, Weiss Hall, 1701 N. 13th Street, Philadelphia, PA 19122, United States.
Emre
E
Yildirim
Department of Psychology, Neuroscience Program, Temple University, Weiss Hall, 1701 N. 13th Street, Philadelphia, PA 19122, United States.
Rachel L F
RL
Poole
Department of Psychology, Neuroscience Program, Temple University, Weiss Hall, 1701 N. 13th Street, Philadelphia, PA 19122, United States.
Prescott T
PT
Leach
Department of Psychology, Neuroscience Program, Temple University, Weiss Hall, 1701 N. 13th Street, Philadelphia, PA 19122, United States.
Steven J
SJ
Simmons
D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D008297:Male; D057567:Memory, Long-Term / Q000187:drug effects* / Q000502:physiology; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*
D018722:Nicotinic Agonists; D009538:Nicotine; D017868:Cyclic AMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
Acetylcholine; Addiction; Learning; Plasticity; Protein synthesis