Extracellular signal-regulated kinase 1/2 involvement in the enhancement of contextual fear conditioning by nicotine

Abstract

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.