In vivo nicotine treatment regulates mesocorticolimbic CREB and ERK signaling in C57Bl/6J mice.
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 C57Bl/6J mice received acute or chronic nicotine (200 microg/mL) in their drinking water or were withdrawn from nicotine for 24 h following chronic exposure.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.
Brunzell
Darlene H
DH
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.
Russell
David S
DS
Picciotto
Marina R
MR
D000284:Administration, Oral; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D003367:Cotinine / Q000097:blood; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004334:Drug Administration Schedule; D008032:Limbic System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008636:Mesencephalon / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009538:Nicotine / Q000097:blood / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014029:Tobacco Use Disorder / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D018722:Nicotinic Agonists; D009538:Nicotine; D020928:Mitogen-Activated Protein Kinases; D003367:Cotinine