Extracellular signal-regulated kinase 1/2 involvement in the enhancement of contextual fear conditioning by nicotine.
Contextual fear conditioning is enhanced by nicotine, but the cellular mechanisms underlying this effect are unknown. Extracellular signal regulated kinase 1/2 (ERK 1/2) has been shown to play an integral role in the formation of contextual fear memories. As such, it is possible that ERK 1/2 is involved in the enhancement of contextual fear conditioning by nicotine. To determine whether ERK 1/2 plays a role in this enhancement, a dose of SL327 (a selective, systemic ERK 1/2 inhibitor) that is subthreshold for inhibiting contextual fear conditioning was coadministered with nicotine prior to training, testing, or both training and testing of contextual fear conditioning in C57BL/6 mice. When administered prior to training, this subthreshold dose of SL327 attenuated the enhancement of contextual fear conditioning by nicotine to levels similar to those of vehicle-treated animals. When administered prior to testing, the subthreshold dose of SL327 did not significantly alter conditioning. These results suggest that activation of ERK 1/2 by nicotine during acquisition leads to an enhancement of contextual fear conditioning.
Raybuck
Jonathan D
JD
Department of Psychology, Temple University, Philadelphia, PA 19122, USA.
Gould
Thomas J
TJ
D000607:Aminoacetonitrile / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005239:Fear / Q000187:drug effects* / Q000523:psychology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D018722:Nicotinic Agonists; C424127:SL 327; D000607:Aminoacetonitrile; D009538:Nicotine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3