Alcohol Relapse Induced by Discrete Cues Activates Components of AP-1 Transcription Factor and ERK Pathway in the Rat Basolateral and Central Amygdala

Radwańska, Kasia; Wróbel, Elżbieta; Korkosz, Agnieszka; Rogowski, Artur; Kostowski, Wojciech; Bieńkowski, Przemysław; Kaczmarek, Leszek

doi:10.1038/sj.npp.1301567

Cited by 60 publications

(52 citation statements)

References 70 publications

(102 reference statements)

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“…ERK in the amygdala also appears to be critically involved in the long-term neuroadaptations which result in heightened reactivity to drug-associated cues. This is supported by the observation that reexposure to an ethanol-associated context and discrete cues following abstinence increases activation of ERK in the BLA and ventral lateral amygdala (Radwanska et al, 2008). Collectively, these findings indicate that activation of ERK, particularly in the amygdala appears to be a key substrate for incubation of drug craving.…”

Section: The Role Of Mapk In the Abstinence Model Of Relapse And Incusupporting

confidence: 71%

The Role of Mitogen-Activated Protein Kinase in Treatment Strategies for Fear and Drug Addiction

Brown¹,

Lawrence²,

Kim³

2012

Advances in Protein Kinases

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Section: The Role Of Mapk In the Abstinence Model Of Relapse And Incusupporting

confidence: 71%

The Role of Mitogen-Activated Protein Kinase in Treatment Strategies for Fear and Drug Addiction

Brown¹,

Lawrence²,

Kim³

2012

Advances in Protein Kinases

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“…Exposure to alcohol-related visual cues (Wiers et al, 2015; Wiers et al, 2014) or alcohol odor (Schneider et al, 2001) increases craving and neural activity in the amygdala of abstinent alcohol-dependent patients as measured by fMRI. Rodent studies show that exposure to cues paired with alcohol increases markers of neural activation in the basolateral amygdala including ERK1/2 MAP kinase phosphorylation (Radwanska et al, 2008; Schroeder et al, 2008) and Fos expression (Jupp et al, 2011; Radwanska et al, 2008). Further, cue-induced reinstatement of alcohol-seeking is associated with increased glutamate transmission in the basolateral amygdala (Gass et al, 2011), which should increase intracellular Ca 2+ that binds calmodulin and promotes activation of CaMKII via phosphorylation at T286.…”

Section: Discussionmentioning

confidence: 99%

Cue-induced reinstatement of alcohol-seeking behavior is associated with increased CaMKII T286 phosphorylation in the reward pathway of mice

Salling

et al. 2017

Pharmacology Biochemistry and Behavior

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Cue-induced reinstatement of alcohol-seeking is a hallmark behavioral pathology of addiction. Evidence suggests that reinstatement (e.g., relapse), may be regulated by cell signaling systems that underlie neuroplasticity. A variety of plasticity events require activation of calcium calmodulin-dependent protein kinase II (CaMKII) in components of the reward pathway, such as the nucleus accumbens and amygdala. We sought to determine if cue-induced reinstatement of alcohol-seeking behavior is associated with changes in the activation state (e.g., phosphorylation) of CaMKII-T286. Male C57BL/6J mice (n = 14) were trained to lever press on a fixed-ratio-4 schedule of sweetened alcohol (2% sucrose + 9% EtOH) reinforcement. After 14-d of extinction (no cues or reinforcers), mice underwent a response-contingent reinstatement (n = 7) vs. an additional day of extinction (n = 7). Brains were removed immediately after the test and processed for evaluation of pCaMKII-T286 immunoreactivity (IR). Number of pCaMKII-T286 positive cells/mm2 was quantified from coronal brain sections using Bioquant Image Analysis software. Mice emitted significantly more responses on the alcohol vs. the inactive lever throughout the baseline phase with average alcohol intake of 1.1 ± 0.03 g/kg/1-h. During extinction, responses on the alcohol lever decreased to inactive lever levels by day 7. Significant cue-induced reinstatement of alcohol-seeking was observed during a single test with no effects on the inactive lever. Reinstatement was associated with increased pCaMKII-T286 IR specifically in amygdala (LA and BLA), nucleus accumbens (AcbSh), lateral septum, mediodorsal thalamus, and piriform cortex as compared to extinction control. Brain regions showing no change included the dorsal striatum, medial septum, cingulate cortex, habenula, paraventricular thalamus, and ventral hypothalamus. These results show response contingent cue-induced reinstatement of alcohol-seeking behavior is associated with selective increases in pCaMKII-T286 in specific reward- and memory-related brain regions of male C57BL/6J mice. Primary molecular mechanisms of associative learning and memory may regulate relapse in alcohol addiction.

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“…In ethanol dependent rats, neuroadaptations encompassing MEK/ERK signaling occur in a region-specific manner (Hansson et al, 2008). Additionally, relapse-inducing cues activated ERK1/2 signaling in the basolateral amygdala of rats previously trained to self-administer ethanol (Radwanska et al, 2008). …”

Section: Discussionmentioning

confidence: 99%

Dual‐Trait Selection for Ethanol Consumption and Withdrawal: Genetic and Transcriptional Network Effects

Metten

Iancu

Spence

et al. 2014

Alcoholism Clin & Exp Res

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Background Data from C57BL/6J (B6) × DBA/2J (D2) F2 intercrosses (B6×D2 F2), standard and recombinant inbred strains, and heterogeneous stock mice indicate that a reciprocal (or inverse) genetic relationship exists between alcohol consumption and withdrawal severity. Furthermore, some genetic studies have detected reciprocal quantitative trait loci (QTLs) for these traits. We used a novel mouse model developed by simultaneous selection for both high alcohol consumption/low withdrawal and low alcohol consumption/high withdrawal and analyzed the gene expression and genome-wide genotypic differences. Methods Randomly chosen third selected generation (S3) mice (N=24/sex/line), bred from a B6×D2 F2, were genotyped using the Mouse Universal Genotyping Array, which provided 2,760 informative markers. QTL analysis used a marker-by-marker strategy with the threshold for a significant log of the odds (LOD) set at 10. Gene expression in the ventral striatum was measured using the Illumina Mouse 8.2 array. Differential gene expression and the weighted gene coexpression network analysis (WGCNA) were implemented. Results Significant QTLs for consumption/withdrawal were detected on Chromosomes (Chr) 2, 4, 9, and 12. A suggestive QTL mapped to Chr 6. Some of the QTLs overlapped with known QTLs mapped for one of the traits individually. 1745 transcripts were detected as being differentially expressed between the lines; there was some overlap with known withdrawal genes (e.g. Mpdz) located within QTL regions. WGCNA revealed several modules of co-expressed genes showing significant effects in both differential expression and intramodular connectivity; a module richly annotated with kinase-related annotations was most affected. Discussion Marked effects of selection on expression and network structure were detected. QTLs overlapping with differentially expressed genes on Chr 2 (distal) and 4 suggest that these are cis-eQTLs (Chr 2: Kif3b, Kcnq2; Chr 4: Mpdz, Snapc3). Other QTLs identified were on Chr 2 (proximal), 9, and 12. Network results point to involvement of kinase-related mechanisms and outline the need for further efforts such as interrogation of non-coding RNAs.

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Alcohol Relapse Induced by Discrete Cues Activates Components of AP-1 Transcription Factor and ERK Pathway in the Rat Basolateral and Central Amygdala

Cited by 60 publications

References 70 publications

The Role of Mitogen-Activated Protein Kinase in Treatment Strategies for Fear and Drug Addiction

The Role of Mitogen-Activated Protein Kinase in Treatment Strategies for Fear and Drug Addiction

Cue-induced reinstatement of alcohol-seeking behavior is associated with increased CaMKII T286 phosphorylation in the reward pathway of mice

Dual‐Trait Selection for Ethanol Consumption and Withdrawal: Genetic and Transcriptional Network Effects

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