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

Abstract

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/Ca 2+ -activated tyrosine kinase (PYK2), and levels of tyrosine hydroxylase (TH), were determined using western blotting. C57Bl/6J mice received acute or chronic nicotine (200 lg/mL) in their drinking water or were withdrawn from nicotine for 24 h following chronic exposure.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.

Short‐Term E‐Cigarette Exposure Increases the Risk of Thrombogenesis and Enhances Platelet Function in Mice

“…These findings suggest that the G 12/13 96 and G i 97 signaling pathways are involved, respectively, and provide biochemical evidence of the hyperactive state of platelets. These data are also consistent with previous studies in which both the Akt98 and ERK99, 100 pathways were upregulated by nicotine.…”

β-Arrestins 1 and 2 are associated with nicotine dependence in European American smokers

“…b-Arrestins 1 and 2 are associated with ND D Sun et al roles in the opioid receptor and MAPK signaling transduction processes [24][25][26]46 and the extensive evidence that opioid receptors and MAPK cascades are involved in drug addiction, [18][19][20][21][22][27][28][29][30] ARRB1 and ARRB2 were considered plausible candidates for ND.…”

“…MAPK has been implicated in mediating the reinforcing effects of drugs of abuse and the neural plasticity associated with various addictive drugs. [27][28][29][30] However, no published studies exist examining the direct association between b-arrestins and drug addiction. Terwilliger et al 31 reported that chronic morphine administration increases b-arrestin levels in the rat locus coeruleus.…”

Linkage and association studies in African- and Caucasian-American populations demonstrate that SHC3 is a novel susceptibility locus for nicotine dependence

“…This is primarily because both the MAPK pathway and NMDARs have been demonstrated to play a crucial role in neural development, synaptic plasticity, learning and memory, and are regulated by various addictive drugs including nicotine, ethanol, cocaine, morphine and tetrahydrocannabinol. 18,[43][44][45][46][47] Further, many recent reports have shown that activation of the extracellular signal-regulated kinase pathway (ERK), an important member of the MAPK pathway, depends on both dopamine receptors (e.g., D1) and NMDARs in the regions involving reward circuitry innervated by dopamine neurons. 20,46,48,49 It is likely that the mechanism underlying regulation of Shc3 by nicotine is the specific modulation of the phosphorylation state of ERK by stimulation of dopamine secretion and expression of dopamine or glutamate receptors in the dopaminergic areas.…”

“…SHC3 is expressed predominantly in the mature neurons of the central nervous system (CNS) and transmits neurotrophin signals from the TrkB receptor to the Ras/mitogen-activated protein kinase (MAPK) pathway, 15,16 which has been implicated in both the reinforcing effects of drugs of abuse and the neural plasticity associated with various addictive drugs. [17][18][19][20] With ShcC-null mice, it was found that the gene not only mediates TrkB-Ras/MAPK signaling but also is involved in the regulation of N-methyl-Daspartate receptor (NMDAR) function. 21 Furthermore, a recent study revealed a novel function of Shc3 in the regulation of the neuronal adaptive response to environmental stress, suggesting that Shc3 functions as a stress-response gene that increases phosphatidylinositol 3-kinase activation and Akt phosphorylation after hypoxic or oxidation insults.…”