scholarly journals PHOSPHORYLATION OF CALCIUM/CALMODULIN-DEPENDENT PROTEIN KINASE II (CAMKII) AND EXTRACELLULAR REGULATED KINASE (ERK) IN STRIATUM MEDIATE NICOTINE DEPENDENCE IN BALB/C MICE

2021 ◽  
pp. 95-99
Author(s):  
GOFARANA WILAR ◽  
KOHJI FUKUNAGA
Keyword(s):  
Conditioned Place Preference ◽  
Nicotine Dependence ◽  
Place Preference ◽  
Erk Signaling ◽  
Rewarding Effect ◽  
Calcium Calmodulin Dependent ◽  
Erk Phosphorylation ◽  
Extracellular Signal ◽  
Dependent Protein ◽  
Molecular Substrates

Objective: Nicotine is an active compound in tobacco and has a rewarding effect in the central nervous system (CNS), which may lead to dependence. Although nicotine dependence is elucidated by brain mechanisms, synaptic molecular substrates underlying the dependence remain unclear. We hypothesized that reward signaling is mediated by dopamine and glutamate receptors, in where calcium/calmodulin-dependent kinase II (CaMKII) and extracellular signal-regulated kinase (ERK) may mediate the synaptic signaling of dependence. Methods: To investigate the roles of both CaMKII and ERK on nicotine dependence were assessed by conditioned place preference (CPP) methods followed by dissection. One day after conditioning, preference scores were measured to evaluate nicotine dependence. Mice were sacrificed and their striatum were dissected out for immunoblotting analyses of CaMKII and ERK phosphorylation. Results: Nicotine-induced conditioned place preference as a symptom of nicotine dependence. CaMKII and ERK phosphorylation in striatum significantly increased along with the development of nicotine dependence. Conclusion: We should next apply pharmacological strategies to manipulate CaMKII and ERK signaling. In particular, disruption of reconsolidation by disrupting CaMKII and ERK signaling may propose an attractive therapeutic approach to inhibit nicotine dependence.

Evidence for the involvement of CaMKII and AMPK in Ca2+-dependent signaling pathways regulating FA uptake and oxidation in contracting rodent muscle

2008 ◽  
Vol 104 (5) ◽  
pp. 1366-1373 ◽  
Author(s):  
Marcella A. Raney ◽  
Lorraine P. Turcotte
Keyword(s):  
Electrical Stimulation ◽  
Protein Kinase ◽  
Dependent Protein Kinase ◽  
Extracellular Signal Regulated Kinase ◽  
Calcium Calmodulin Dependent ◽  
Extracellular Signal ◽  
Regulation Of Contraction ◽  
Dependent Protein ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

Calcium-calmodulin/dependent protein kinase II (CaMKII), AMP-activated protein kinase (AMPK), and extracellular signal-regulated kinase (ERK1/2) have each been implicated in the regulation of substrate metabolism during exercise. The purpose of this study was to determine whether CaMKII is involved in the regulation of FA uptake and oxidation and, if it is involved, whether it does so independently of AMPK and ERK1/2. Rat hindquarters were perfused at rest with ( n = 16) or without ( n = 10) 3 mM caffeine, or during electrical stimulation ( n = 14). For each condition, rats were subdivided and treated with 10 μM of either KN92 or KN93, inactive and active CaMKII inhibitors, respectively. Both caffeine treatment and electrical stimulation significantly increased FA uptake and oxidation. KN93 abolished caffeine-induced FA uptake, decreased contraction-induced FA uptake by 33%, and abolished both caffeine- and contraction-induced FA oxidation ( P < 0.05). Caffeine had no effect on ERK1/2 phosphorylation ( P > 0.05) and increased α2-AMPK activity by 68% ( P < 0.05). Electrical stimulation increased ERK1/2 phosphorylation and α2-AMPK activity by 51% and 3.4-fold, respectively ( P < 0.05). KN93 had no effect on caffeine-induced α2-AMPK activity, ERK1/2 phosphorylation, or contraction-induced ERK1/2 phosphorylation ( P > 0.05). Alternatively, it decreased contraction-induced α2-AMPK activity by 51% ( P < 0.05), suggesting that CaMKII lies upstream of AMPK. These results demonstrate that regulation of contraction-induced FA uptake and oxidation occurs in part via Ca2+-independent activation of ERK1/2 as well as Ca2+-dependent activation of CaMKII and AMPK.

8-pCPT, an Epac activator, impairs conditioned place preference based on nucleus accumbens amphetamine in rats

2013 ◽  
Vol 26 (2) ◽  
pp. 104-111 ◽  
Author(s):  
Sung Woo Park ◽  
Ali Roohbakhsh ◽  
Richard J. Beninger
Keyword(s):  
Nucleus Accumbens ◽  
Protein Kinase ◽  
Dopamine Receptor ◽  
Conditioned Place Preference ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Place Preference ◽  
Dependent Protein Kinase ◽  
Cyclic Monophosphate ◽  
Dependent Protein

ObjectivesDopamine receptor-mediated 3′,5′-cyclic adenosine monophosphate (cAMP)-dependent intracellular signalling is important for reward-related learning. cAMP activates cAMP-dependent protein kinase (PKA) and exchange protein directly activated by cAMP (Epac). We tested the hypothesis that reward-related learning may be mediated by Epac.MethodsWe evaluated conditioned place preference (CPP) on the basis of nucleus accumbens (NAc) injections of amphetamine (20 μg/0.5 μl/side) plus Sp-adenosine 3′,5′-cyclic monophosphorothioate triethylamanine (Sp-cAMPS) (0.1, 1.0, 10, 15, 20 μg/0.5 μl/side), an activator of both PKA and Epac, or amphetamine (20 μg) plus 8-(4-chlorophenylthio)-2′-O-methyladenosine-3′,5′-cyclic monophosphate (8-pCPT) (0.73, 1.27, 1.45, 2.89, 5.78, 11.56 μg/0.5 μl/side), an activator of Epac.ResultsIn agreement with previous results, Sp-cAMPS dose-dependently impaired CPP. 8-pCPT impaired CPP at one dose (1.45 μg/0.5 μl/side) and we replicated this effect three times.ConclusionThe results implicate Epac in the acquisition of reward-related learning.

Effects of caffeine on ethanol-elicited place preference, place aversion and ERK phosphorylation in CD-1 mice

2020 ◽  
Vol 34 (12) ◽  
pp. 1357-1370
Author(s):  
Simona Porru ◽  
Riccardo Maccioni ◽  
Valentina Bassareo ◽  
Alessandra T Peana ◽  
John D Salamone ◽  
...  
Keyword(s):  
Associative Learning ◽  
Conditioned Place Preference ◽  
Place Preference ◽  
Conditioned Place Aversion ◽  
Brain Areas ◽  
Pharmacological Interaction ◽  
Place Aversion ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Kinase Phosphorylation

Background: Epidemiological studies indicate a rise in the combined consumption of caffeinated and alcoholic beverages, which can lead to increased risk of alcoholic-beverage overconsumption. However, the effects of the combination of caffeine and ethanol in animal models related to aspects of drug addiction are still underexplored. Aims: To characterize the pharmacological interaction between caffeine and ethanol and establish if caffeine can affect the ability of ethanol (2 g/kg) to elicit conditioned place preference and conditioned place aversion, we administered caffeine (3 or 15 mg/kg) to male CD-1 mice before saline or ethanol. Moreover, we determined if these doses of caffeine could affect ethanol (2 g/kg) elicited extracellular signal-regulated kinase phosphorylation in brain areas, nucleus accumbens, bed nucleus of stria terminalis, central nucleus of the amygdala, and basolateral amygdala, previously associated with this type of associative learning. Results: In the place-conditioning paradigm, caffeine did not have an effect on its own, whereas ethanol elicited significant conditioned-place preference and conditioned-place aversion. Caffeine (15 mg/kg) significantly prevented the acquisition of ethanol-elicited conditioned-place preference and, at both doses, also prevented the acquisition of ethanol-elicited conditioned-place aversion. Moreover, both doses of caffeine also prevented ethanol-elicited extracellular signal-regulated kinase phosphorylation expression in all brain areas examined. Conclusions: The present data indicate a functional antagonistic action of caffeine and ethanol on associative learning and extracellular signal-regulated kinase phosphorylation after an acute interaction. These results could provide exciting grounds for further studies, also in a translational perspective, of their pharmacological interaction modulating other processes involved in drug consumption and addiction.

scholarly journals Cocaine-dependent acquisition of locomotor sensitization and conditioned place preference requires D1 dopaminergic signaling through a cyclic AMP, NCS-Rapgef2, ERK and Egr-1/Zif268 pathway

2020 ◽  
Author(s):  
Sunny Zhihong Jiang ◽  
Sean Sweat ◽  
Sam Dahlke ◽  
Kathleen Loane ◽  
Gunner Drossel ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Conditioned Place Preference ◽  
Mouse Brain ◽  
Place Preference ◽  
Dopamine D1 Receptor ◽  
D1 Receptor ◽  
Locomotor Sensitization ◽  
Erk Activation ◽  
Erk Phosphorylation ◽  
Dopamine Signaling

ABSTRACTElucidation of the underlying mechanism of dopamine signaling to ERK that underlies plasticity in dopamine D1 receptor expressingneurons leadingto acquired cocaine preference is incomplete. NCS-Rapgef2 is a novel cAMP effector, expressed in neuronal and endocrine cells in adult mammals, that is required for D1 dopamine receptor-dependent ERK phosphorylation in mouse brain. In this report, we studied the effects of abrogating NCS-Rapgef2 expression on cAMP-dependent ERK→Egr-1/zif268 signaling in cultured neuroendocrine cells; in D1 medium spiny neurons (MSNs) of nucleus accumbens slices; and in mouse brain in a region-specific manner. NCS-Rapgef2 gene deletion in the nucleus accumbens (NAc) in adult mice, using AAV-mediated expression of cre recombinase, eliminated cocaine-induced ERK phosphorylation and Egr-1/Zif268 upregulation in D1-MSNs and cocaine-induced behaviors including locomotor sensitization and conditioned place preference (CPP). Abrogation of NCS-Rapgef2 gene expression in medium prefrontal cortex and basolateral amygdala, by crossing mice bearing a floxed Rapgef2 allele with a cre mouse line driven by calcium/calmodulin-dependent kinase IIα promoter also eliminated cocaine-induced phospho-ERK activation and Egr-1/Zif268 induction, but without effect on the cocaine-induced behaviors. Our results indicate that NCS-Rapgef2 signaling to ERK in dopamine D1-receptor expressing neurons in the NAc, butnotin corticolimbic areas, contributes to cocaine-induced locomotor sensitization and CPP. Ablation of cocaine-dependent ERK activation by elimination of NCS-Rapgef2 occurred with no effect on phosphorylation of CREB in D1 dopaminoceptive neurons of NAc. This study reveals a new cAMP-dependent signaling pathway for cocaine-induced behavioral adaptations, mediated through NCS-Rapgef2/phospho-ERK activation, independently of PKA/CREB signaling.SIGNIFICANCE STATEMENTERK phosphorylation in dopamine D1 receptor expressing neurons exerts a pivotal role in psychostimulant-induced neuronal gene regulation and behavioraladaptation, including locomotor sensitization and drug preference in rodents. In this study, we examined the role of dopamine signaling through the D1 receptor via a novel pathway initiated through the cAMP-activated guanine nucleotide exchange factor NCS-Rapgef2 in mice. NCS-Rapgef2 in the nucleus accumbens is required for activation of ERK and Egr-1/Zif268 in D1 dopaminoceptive neurons after acute cocaine administration, and subsequentenhanced locomotor response anddrugseeking behavior after repeated cocaine administration. This novel component in dopamine signaling provides a potential new target for intervention in psychostimulant-shaped behaviors, and new understanding of how D1-MSNs encode the experience of psychomotor stimulant exposure.

scholarly journals Extracellular Signal-Regulated Kinase Promotes Rho-Dependent Focal Adhesion Formation by Suppressing p190A RhoGAP

2010 ◽  
Vol 30 (13) ◽  
pp. 3233-3248 ◽  
Author(s):  
Ashok K. Pullikuth ◽  
Andrew D. Catling
Keyword(s):  
Adhesion Formation ◽  
Rho Kinase ◽  
Focal Adhesions ◽  
Mitogen Activated Protein Kinase ◽  
Erk Signaling ◽  
Extracellular Signal Regulated Kinase ◽  
Erk Phosphorylation ◽  
C Terminus ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

ABSTRACT Cell migration is critical for normal development and for pathological processes including cancer cell metastasis. Dynamic remodeling of focal adhesions and the actin cytoskeleton are crucial determinants of cell motility. The Rho family and the mitogen-activated protein kinase (MAPK) module consisting of MEK-extracellular signal-regulated kinase (ERK) are important regulators of these processes, but mechanisms for the integration of these signals during spreading and motility are incompletely understood. Here we show that ERK activity is required for fibronectin-stimulated Rho-GTP loading, Rho-kinase function, and the maturation of focal adhesions in spreading cells. We identify p190A RhoGAP as a major target for ERK signaling in adhesion assembly and identify roles for ERK phosphorylation of the C terminus in p190A localization and activity. These observations reveal a novel role for ERK signaling in adhesion assembly in addition to its established role in adhesion disassembly.

Sign in / Sign up

Export Citation Format

Share Document