Chronic cocaine abusers have occult insomnia in early abstinence

2008 ◽  
Author(s):  
Lori Whitten
Keyword(s):  
Chronic Cocaine

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.

scholarly journals Noradrenergic correlates of chronic cocaine craving: neuromelanin and functional brain imaging

2021 ◽  
Author(s):  
Wuyi Wang ◽  
Simon Zhornitsky ◽  
Sheng Zhang ◽  
Chiang-shan R. Li
Keyword(s):  
Functional Brain Imaging ◽  
Cocaine Exposure ◽  
Imaging Data ◽  
Significant Group ◽  
Motivated Behavior ◽  
Chronic Cocaine ◽  
Cocaine Craving ◽  
Lc Circuit ◽  
Psychophysiological Interaction ◽  
Subcortical Regions

AbstractPreclinical studies have implicated noradrenergic (NA) dysfunction in cocaine addiction. In particular, the NA system plays a central role in motivated behavior and may partake in the regulation of craving and drug use. Yet, human studies of the NA system are scarce, likely hampered by the difficulty in precisely localizing the locus coeruleus (LC). Here, we used neuromelanin imaging to localize the LC and quantified LC neuromelanin signal (NMS) intensity in 44 current cocaine users (CU; 37 men) and 59 nondrug users (NU; 44 men). We also employed fMRI to investigate cue-induced regional responses and LC functional connectivities, as quantified by generalized psychophysiological interaction (gPPI), in CU. Imaging data were processed by published routines and the findings were evaluated with a corrected threshold. We examined how these neural measures were associated with chronic cocaine craving, as assessed by the Cocaine Craving Questionnaire (CCQ). Compared to NU, CU demonstrated higher LC NMS for all probabilistic thresholds defined of 50–90% of the peak. In contrast, NMS of the ventral tegmental area/substantia nigra (VTA/SN) did not show significant group differences. Drug as compared to neutral cues elicited higher activations of many cortical and subcortical regions, none of which were significantly correlated with CCQ score. Drug vs. neutral cues also elicited “deactivation” of bilateral parahippocampal gyri (PHG) and PHG gPPI with a wide array of cortical and subcortical regions, including the ventral striatum and, with small volume correction, the LC. Less deactivation of the PHG (r = 0.40, p = 0.008) and higher PHG-LC gPPI (r = 0.44, p = 0.003) were positively correlated with the CCQ score. In contrast, PHG-VTA/SN connectivity did not correlate with the CCQ score. Together, chronic cocaine exposure may induce higher NMS intensity, suggesting neurotoxic effects on the LC. The correlation of cue-elicited PHG LC connectivity with CCQ score suggests a noradrenergic correlate of chronic cocaine craving. Potentially compensating for memory functions as in neurodegenerative conditions, cue-elicited PHG LC circuit connectivity plays an ill-adaptive role in supporting cocaine craving.

scholarly journals Persistent changes in exploration and hyperactivity coexist with cognitive impairment in mice withdrawn from chronic cocaine

2021 ◽  
pp. 113542
Author(s):  
M. Carmen Mañas-Padilla ◽  
Fabiola Ávila-Gámiz ◽  
Sara Gil-Rodríguez ◽  
David Ladrón de Guevara-Miranda ◽  
Fernando Rodríguez de Fonseca ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Chronic Cocaine

Cardiovascular Effects of Acute and Chronic Cocaine Administration in Pregnant and Nonpregnant Rabbits

1999 ◽  
Vol 158 (3) ◽  
pp. 278-287 ◽  
Author(s):  
Roy L. Sutliff ◽  
Pamela A. Gayheart-Walsten ◽  
David L. Snyder ◽  
Jay Roberts ◽  
Mark D. Johnson
Keyword(s):  
Cardiovascular Effects ◽  
Cocaine Administration ◽  
Chronic Cocaine

scholarly journals Oxytocin Reduces Cocaine Seeking and Reverses Chronic Cocaine-Induced Changes in Glutamate Receptor Function

2014 ◽  
Vol 18 (1) ◽  
pp. pyu009-pyu009 ◽  
Author(s):  
L. Zhou ◽  
W.-L. Sun ◽  
A. B. Young ◽  
K. Lee ◽  
J. F. McGinty ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
Receptor Function ◽  
Chronic Cocaine ◽  
Cocaine Seeking ◽  
Induced Changes

scholarly journals Left ventricular hypertrophy associated with chronic cocaine abuse.

Circulation ◽  
1991 ◽  
Vol 84 (3) ◽  
pp. 1130-1135 ◽  
Author(s):  
M E Brickner ◽  
J E Willard ◽  
E J Eichhorn ◽  
J Black ◽  
P A Grayburn
Keyword(s):  
Left Ventricular Hypertrophy ◽  
Cocaine Abuse ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Chronic Cocaine
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