scholarly journals Previous cocaine self-administration disrupts reward expectancy encoding in ventral striatum

2018 ◽  
Vol 43 (12) ◽  
pp. 2350-2360 ◽  
Author(s):  
Amanda C. Burton ◽  
Gregory B. Bissonette ◽  
Daniela Vazquez ◽  
Elyse M. Blume ◽  
Maria Donnelly ◽  
...  
2020 ◽  
Author(s):  
Laia Alegre-Zurano ◽  
Miguel Á. Luján ◽  
Lídia Cantacorps ◽  
Ana Martín-Sánchez ◽  
Alba García-Baos ◽  
...  

ABSTRACTBackground and PurposeTo remain abstinent represents one of the major challenges for the treatment of cocaine use disorder. Cocaine seeking elicited by drug-associated cues progressively intensifies during abstinence in a process termed incubation of craving, representing an aggravating factor for relapse. Cannabidiol is a phytocannabinoid that exerts protecting effects upon cocaine-seeking behaviour, although its effects on cocaine-craving incubation have never been elucidated.Experimental ApproachWe developed a mouse model of behavioural economic analysis of demand curves and incubation of cue-induced cocaine craving. Changes in the protein expression of AMPAR subunits and ERK1/2 phosphorylation were analysed. We also assessed the effects of cannabidiol (20 mg·kg-1) administered either during acquisition of cocaine self-administration or abstinence.Key ResultsMice efficiently performed the demand task and incubation of cocaine craving. Besides, changes in GluA1 and GluA2 protein levels were found along the abstinence in prelimbic cortex, ventral striatum and amygdala, as well as a decrease in ERK1/2 phosphorylation in ventral striatum. Cannabidiol reduced ongoing cocaine intake when administered during the acquisition phase of the self-administration, but failed to alter the subsequent demand task performance and incubation of cocaine craving. No effects were found when cannabidiol was administered during the abstinence period.Conclusion and ImplicationsWe provide here a novel model of behavioural economic analysis of demand curves and cue-induced incubation of cocaine-seeking behaviour for mice. Moreover, we show that cannabidiol exerts differential effects on the current model depending on the self-administration phase in which it was administered.What is already knownBehavioural economics and incubation of cocaine craving are well-stablished paradigms to evaluate cocaine seeking in rats.CBD reduces cocaine-seeking and cocaine-taking behaviours.What this study addsA mouse model of behavioural economic analysis of demand curves and incubation of cue-induced cocaine craving.CBD reduces cocaine self-administration and has no effect over demand task and cocaine-craving incubation.Clinical significanceA new behavioural model for studying cocaine addiction in mice.CBD exerts differential effects depending on when it was administered in the addictive process.Tables of Links


Author(s):  
Katherine N. Wright ◽  
Daniel W Wesson

The ventral striatum regulates motivated behaviors which are essential for survival. The ventral striatum contains both the nucleus accumbens (NAc), which is well established to contribute to motivated behavior, and the adjacent tubular striatum (TuS), which is poorly understood in this context. We reasoned that these ventral striatal subregions may be uniquely specialized in their neural representation of goal-directed behavior. To test this, we simultaneously examined TuS and NAc single-unit activity as male mice engaged in a sucrose self-administration task, which included extinction and cue-induced reinstatement sessions. While background levels of activity were comparable between regions, more TuS neurons were recruited upon reward-taking, and among recruited neurons, TuS neurons displayed greater changes in their firing during reward-taking and extinction than those in the NAc. Conversely, NAc neurons displayed greater changes in their firing during cue-reinstated reward-seeking. Interestingly, at least in the context of this behavioral paradigm, TuS neural activity predicted reward-seeking whereas NAc activity did not. Together, by directly comparing their dynamics in several behavioral contexts, this work reveals that the NAc and TuS ventral striatum subregions distinctly represent reward-taking and seeking.


2020 ◽  
Vol 44 (6) ◽  
pp. 1224-1233
Author(s):  
Aaron C. Lim ◽  
ReJoyce Green ◽  
Erica N. Grodin ◽  
Alexandra Venegas ◽  
Lindsay R. Meredith ◽  
...  

2017 ◽  
Vol 171 ◽  
pp. e224
Author(s):  
Yong Zhang ◽  
Yupu Liang ◽  
Matthew Randesi ◽  
Orna Levran ◽  
Vadim Yuferov ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kyoungjune Pak ◽  
Ju Won Seok ◽  
Hyun-Yeol Nam ◽  
Seongho Seo ◽  
Myung Jun Lee ◽  
...  

Abstract Background DNA methylation inhibits gene expression by preventing transcription factors from binding to DNA. Functioning of nigrostriatal dopaminergic neurons is influenced by the expression of the dopamine transporter (DAT), and genetic variations in the gene encoding DAT contribute to differences in reward processing. We aimed to investigate the action of DAT methylation on DAT protein expression measured by positron emission tomography (PET). Methods The emission data were acquired over 90 min with 50 frames after injection of 18F-FP-CIT using PET. Binding potentials (BPNDs) of ventral striatum, caudate nucleus, putamen were measured with the simplified reference tissue method. Genomic DNA was extracted from subjects’ blood sampling. Methylation of 4 regions in SLC6A3 gene was assessed using bisulfite pyrosequencing. The mean percentage of methylation (%) for each cluster was calculated by taking the average of all CpG site methylation levels measured within the cluster. Subjects were assessed with the Generalized Reward and Punishment Expectancy Scales (GRAPES) that consists of 30 items related with the reward and punishment that individuals expect for their behaviors. Results Thirty-five healthy males, with an age range between 20 and 30 years, and a mean age of 24.4 ± 2.7 years, were included in this study. The mean percentage of methylation (%) from cluster C showed a trend of positive correlation with DAT availability of ventral striatum (rho = 0.3712, p = 0.0281), not significant after correction for multiple comparisons, and a significant correlation with GRAPES A: reward expectancy scale (rho = 0.7178, p < 0.0001). Conclusion DAT methylation from peripheral blood showed a trend of positive correlation with DAT availability of ventral striatum in healthy subjects; however, it was not significant after correction for multiple comparison. The degrees of methylation from cluster C of DAT in peripheral blood were significantly correlated with reward scales of GRAPES A: reward expectancy scale. The association between DAT methylation and DAT expression needs to be investigated further.


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