Differential effects of acute and chronic nicotine on Elk-1 in rat hippocampus.

Transcriptional regulation is central to the long-term effects of drugs of abuse. Activation of the extracellular signal-regulated kinase (ERK1/2) pathway underlies plasticity changes that accompany drug use. One target of ERK1/2 activation is the Ets-like transcription factor Elk-1. We show here that nicotine modulates Elk-1 in the rat hippocampus in a spatially and temporally specific manner. In-vitro nicotine (1 muM) activated Elk-1 in hippocampal slices. In-vivo acute nicotine (0.4 mg/kg) activated Elk-1 in the CA1 area but not in the dentate gyrus. Chronic nicotine for 14 days changed the level of total Elk-1 but not its phosphorylation state. Thus, Elk-1 regulation of transcriptional events may contribute to nicotine-induced changes in the hippocampus.