In vivo nicotine treatment regulates mesocorticolimbic CREB and ERK signaling in C57Bl/6J mice

• Published in: Journal of neurochemistry Vol. 84; no. 6; pp. 1431 - 1441
• Main Authors: Brunzell, Darlene H., Russell, David S., Picciotto, Marina R.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.03.2003
• Subjects: Administration, Oral; amygdala; Amygdala - drug effects; Amygdala - metabolism; Animals; Cotinine - blood; Cyclic AMP Response Element-Binding Protein - metabolism; Drug Administration Schedule; extracellular regulated protein kinase; Limbic System - drug effects; Limbic System - metabolism; Male; Mesencephalon - drug effects; Mesencephalon - metabolism; Mice; Mice, Inbred C57BL; mitogen activated protein kinase; Mitogen-Activated Protein Kinases - metabolism; Nicotine - blood; Nicotine - pharmacology; Nicotinic Agonists - pharmacology; nucleus accumbens; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Phosphorylation - drug effects; prefrontal cortex; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Signal Transduction - drug effects; Tobacco Use Disorder - metabolism; tyrosine hydroxylase; ventral tegmental area; Ventral Tegmental Area - drug effects; Ventral Tegmental Area - metabolism
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2003.01640.x

The extracellular regulated kinase (ERK) pathway was studied to determine its role in neuronal plasticity related to the development of nicotine dependence. Levels and phosphorylation state of ERK, cAMP response element binding protein (CREB) and proline‐rich/Ca2+‐activated tyrosine kinase (PYK2), and levels of tyrosine hydroxylase (TH), were determined using western blotting. C57Bl/6J mice received acute or chronic nicotine (200 µg/mL) in their drinking water or were withdrawn from nicotine for 24 h following chronic exposure. CREB phosphorylation was reduced in the nucleus accumbens following chronic nicotine, consistent with previous reports that decreased accumbens CREB activity increases drug reinforcement. In contrast, CREB phosphorylation was increased in the prefrontal cortex following chronic nicotine exposure and in the ventral tegmental area during nicotine withdrawal. In addition, total and phosphorylated ERK decreased in the amygdala following chronic nicotine exposure, but ERK phosphorylation increased in the prefrontal cortex. TH levels increased in both the amygdala and prefrontal cortex, supporting the hypothesis that increased catecholaminergic tone contributes to nicotine reinforcement. Overall, these results support a role for ERK and CREB activity in neural plasticity associated with nicotine dependence.