A role for the endocannabinoid enzymes monoacylglycerol and diacylglycerol lipases in cue‐induced cocaine craving following prolonged abstinence

2021 ◽  
Author(s):  
Swarup Mitra ◽  
Pedro H. Gobira ◽  
Craig T. Werner ◽  
Jennifer A. Martin ◽  
Madoka Iida ◽  
...  
Keyword(s):  
Cocaine Craving ◽  
Prolonged Abstinence ◽  
Endocannabinoid Enzymes

scholarly journals Ubiquitin-proteasomal regulation of chromatin remodeler INO80 in the nucleus accumbens mediates persistent cocaine craving

2019 ◽  
Vol 5 (10) ◽  
pp. eaay0351 ◽  
Author(s):  
C. T. Werner ◽  
S. Mitra ◽  
J. A. Martin ◽  
A. F. Stewart ◽  
A. E. Lepack ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Ubiquitin Ligase ◽  
Chromatin Immunoprecipitation ◽  
Drug Exposure ◽  
Epigenetic Mechanism ◽  
Chromatin Remodeler ◽  
Self Administration ◽  
Behavioral Abnormalities ◽  
Cocaine Craving ◽  
Prolonged Abstinence

Neuroadaptations in the nucleus accumbens (NAc) underlie cue-induced cocaine craving that intensifies (“incubates”) during abstinence and is believed to contribute to persistent relapse vulnerability. Changes in gene expression often govern perpetual behavioral abnormalities, but epigenetic plasticity during prolonged abstinence from drug exposure is poorly understood. We examined how E3 ubiquitin ligase TRIM3 dysregulates chromatin remodeler INO80 to mediate cocaine craving during prolonged abstinence. We found that INO80 expression increased in the NAc on abstinence day 30 (AD30) but not on AD1 following cocaine self-administration. Furthermore, TRIM3, which mediates degradation of INO80, was reduced on AD30, along with TRIM3-INO80 interaction. Viral-mediated gene transfer of INO80 or TRIM3 governed cocaine craving during prolonged abstinence. Lastly, chromatin immunoprecipitation followed by massively parallel DNA sequencing identified INO80-mediated transcriptional regulation of predicted pathways associated with cocaine plasticity. Together, these results demonstrate a novel ubiquitin-proteasomal-epigenetic mechanism by which TRIM3-INO80 mediates cocaine craving during prolonged abstinence.

Daily and Weekly Patterns in Heroin and Cocaine Craving and Use

2008 ◽  
Author(s):  
Kenzie L. Preston ◽  
Jessica Willner-Reid ◽  
Jia-Ling Lin ◽  
Massoud Vahabzadeh ◽  
David H. Epstein
Keyword(s):  
Cocaine Craving

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 Effects of environmental enrichment on the incubation of cocaine craving

2012 ◽  
Vol 63 (4) ◽  
pp. 635-641 ◽  
Author(s):  
Claudia Chauvet ◽  
Steven R. Goldberg ◽  
Mohamed Jaber ◽  
Marcello Solinas
Keyword(s):  
Environmental Enrichment ◽  
Cocaine Craving

scholarly journals Repeated restraint stress exposure during early withdrawal accelerates incubation of cue-induced cocaine craving

2016 ◽  
Vol 23 (1) ◽  
pp. 80-89 ◽  
Author(s):  
Ryan M. Glynn ◽  
J. Amiel Rosenkranz ◽  
Marina E. Wolf ◽  
Aaron Caccamise ◽  
Freya Shroff ◽  
...  
Keyword(s):  
Restraint Stress ◽  
Stress Exposure ◽  
Early Withdrawal ◽  
Repeated Restraint Stress ◽  
Cocaine Craving

Initial validation of the Voris cocaine craving scale: A preliminary report

1999 ◽  
Vol 55 (1) ◽  
pp. 135-139 ◽  
Author(s):  
David A. Smelson ◽  
Eileen McGee-Caulfield ◽  
Pauline Bergstein ◽  
Charles Engelhart
Keyword(s):  
Preliminary Report ◽  
Initial Validation ◽  
Cocaine Craving

scholarly journals Activation of memory circuits during cue-elicited cocaine craving.

1996 ◽  
Vol 93 (21) ◽  
pp. 12040-12045 ◽  
Author(s):  
S. Grant ◽  
E. D. London ◽  
D. B. Newlin ◽  
V. L. Villemagne ◽  
X. Liu ◽  
...  
Keyword(s):  
Memory Circuits ◽  
Cocaine Craving

scholarly journals Effectiveness of a motivational intervention based on spirometry results to achieve smoking cessation in primary healthcare patients: randomised, parallel, controlled multicentre study

2021 ◽  
pp. jech-2020-216219
Author(s):  
Francisco Martin-Lujan ◽  
Josep Basora-Gallisa ◽  
Felipe Villalobos ◽  
Nuria Martin-Vergara ◽  
Estefania Aparicio-Llopis ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Respiratory Disease ◽  
Primary Healthcare ◽  
Intervention Group ◽  
Control Group ◽  
Smoking Cessation Advice ◽  
Registration Number ◽  
Brief Advice ◽  
Prolonged Abstinence

ObjectiveThis 12-month study in a primary healthcare network aimed to assess the effectiveness of usual smoking cessation advice compared with personalised information about the spirometry results.DesignRandomised, parallel, controlled, multicentre clinical trial.SettingThis study involved 12 primary healthcare centres (Tarragona, Spain).ParticipantsActive smokers aged 35–70 years, without known respiratory disease. Each participant received brief smoking cessation advice along with a spirometry assessment. Participants with normal results were randomised to the intervention group (IG), including detailed spirometry information at baseline and 6-month follow-up or control group (CG), which was simply informed that their spirometry values were within normal parameters.Main outcomeProlonged abstinence (12 months) validated by expired-CO testing.ResultsSpirometry was normal in 571 patients in 571 patients (45.9% male), 286 allocated to IG and 285 to CG. Baseline characteristics were comparable between the groups. Mean age was 49.8 (SD ±7.78) years and mean cumulative smoking exposure was 29.2 (±18.7) pack-years. Prolonged abstinence was 5.6% (16/286) in the IG, compared with 2.1% (6/285) in the CG (p=0.03); the cumulative abstinence curve was favourable in the IG (HR 1.98; 95% CI 1.29 to 3.04).ConclusionsIn active smokers without known respiratory disease, brief advice plus detailed spirometry information doubled prolonged abstinence rates, compared with brief advice alone, in 12-month follow-up, suggesting a more effective intervention to achieve smoking cessation in primary healthcare.Trial registration numberNCT01194596.

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