Role of BRD4 phosphorylation in the nucleus accumbens in relapse to cocaine‐seeking behavior in mice

2019 ◽  
Vol 25 (5) ◽  
Author(s):  
Wei Guo ◽  
Hailei Long ◽  
Qian Bu ◽  
Yinglan Zhao ◽  
Hongbo Wang ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Cocaine Seeking ◽  
Seeking Behavior

Role of GluR1 expression in nucleus accumbens neurons in cocaine sensitization and cocaine-seeking behavior

2008 ◽  
Vol 27 (9) ◽  
pp. 2229-2240 ◽  
Author(s):  
Ryan K. Bachtell ◽  
Kwang-Ho Choi ◽  
Diana L. Simmons ◽  
Edgardo Falcon ◽  
Lisa M. Monteggia ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Cocaine Seeking ◽  
Seeking Behavior

scholarly journals Subregion-specific role of glutamate receptors in the nucleus accumbens on drug context-induced reinstatement of cocaine-seeking behavior in rats

2011 ◽  
Vol 17 (2) ◽  
pp. 287-299 ◽  
Author(s):  
Xiaohu Xie ◽  
Heather C. Lasseter ◽  
Donna R. Ramirez ◽  
KaiCee L. Ponds ◽  
Audrey M. Wells ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Glutamate Receptors ◽  
Specific Role ◽  
Cocaine Seeking ◽  
Seeking Behavior

Dopaminylation in Psychostimulant use Disorder Protects Against Psychostimulant Seeking Behavior by Normalizing Nucleus Accumbens (NAc) Dopamine Expression

2021 ◽  
Vol 09 ◽  
Author(s):  
Kenneth Blum ◽  
Mark S Gold ◽  
Jean L. Cadet ◽  
David Baron ◽  
Abdalla Bowirrat ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Histone H3 ◽  
D2 Receptor ◽  
Reward Processing ◽  
Allelic Polymorphism ◽  
Cocaine Withdrawal ◽  
Src Signaling ◽  
Chronic Cocaine ◽  
Cocaine Seeking ◽  
Seeking Behavior

Background: Repeated cocaine administration changes histone acetylation and methylation on Lys residues and Deoxyribonucleic acid (DNA) within the nucleus accumbens (NAc). Recently Nestler’s group explored histone Arg (R) methylation in reward processing models. Damez-Werno et al. (2016) reported that during investigator and selfadministration experiments, the histone mark protein-R-methyltransferase-6 (PRMT6) and asymmetric dimethylation of R2 on histone H3 (H3R2me2a) decreased in the rodent and cocaine-dependent human NAc. Overexpression of PRMT6 in D2-MSNs in all NAc neurons increased cocaine seeking, whereas PRMT6 overexpression in D1-MSNs protects against cocaine-seeking. Hypothesis: Hypothesizing that dopaminylation (H3R2me2a binding) occurs in psychostimulant use disorder (PSU), and the binding inhibitor Srcin1, like the major DRD2 A2 allelic polymorphism, protects against psychostimulant seeking behavior by normalizing nucleus accumbens (NAc) dopamine expression. Discussion: Numerous publications confirmed the association between the DRD2 Taq A1 allele (30-40 lower D2 receptor numbers) and severe cocaine dependence. Lepack et al. (2020) found that acute cocaine increases dopamine in NAc synapses, results in histone H3 glutamine 5 dopaminylation (H3Q5dop), and consequent inhibition of D2 expression. The inhibition increases with chronic cocaine use and accompanies cocaine withdrawal. They also found that the Src kinase sig-naling inhibitor 1 (Srcin1 or p140CAP) during cocaine withdrawal reduced H3R2me2a binding. Consequently, this inhibited dopaminylation induced a “homeostatic brake.” Conclusion: The decrease in Src signaling in NAc D2-MSNs, like the DRD2 Taq A2 allele, a well-known genetic mechanism protective against SUD normalized nucleus accumbens (NAc) dopamine expression and decreased cocaine reward and motivation to self-administer cocaine. The Srcin1 may be an important therapeutic target.

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