scholarly journals Disrupting D1-NMDA or D2-NMDA receptor heteromerization prevents cocaine’s rewarding effects but preserves natural reward processing

2021 ◽  
Vol 7 (43) ◽  
Author(s):  
Andry Andrianarivelo ◽  
Estefani Saint-Jour ◽  
Paula Pousinha ◽  
Sebastian P. Fernandez ◽  
Anna Petitbon ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Reward Processing ◽  
Natural Reward

scholarly journals Disrupting D2-NMDA receptor heteromerization blocks the rewarding effects of cocaine but preserves natural reward processing

2021 ◽  
Author(s):  
Andry Andrianarivelo ◽  
Estefani Saint-Jour ◽  
Paula Pousinha ◽  
Sebastian P. Fernandez ◽  
Anna Petitbon ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Behavioral Responses ◽  
Underlying Mechanism ◽  
Reward Processing ◽  
Natural Reward ◽  
Therapeutic Value ◽  
Glutamate Transmission ◽  
Dopamine Receptor 1 ◽  
Developmental Phases ◽  
Early Developmental

AbstractAddictive drugs increase dopamine in the nucleus accumbens (NAc), where it persistently shapes excitatory glutamate transmission and hijacks natural reward processing. Herein, we provide evidence, from mice to human, that an underlying mechanism relies on drug-evoked heteromerization of glutamate NMDA receptors (NMDAR) with dopamine receptor 1 (D1R) or 2 (D2R). Using temporally-controlled inhibition of D1R-NMDAR heteromerization, we unraveled their selective implication in early developmental phases of cocaine-mediated synaptic, morphological and behavioral responses. In contrast, preventing D2R-NMDAR heteromerization blocked the persistence of these adaptations. Importantly, interfering with these heteromers spared natural reward processing. Strikingly, we established that D2R-NMDAR complexes exist in human samples and showed that, despite a decreased D2R protein expression in the NAc, psychostimulant-addicts display a higher proportion of D2R forming heteromers with NMDAR. These findings contribute to a better understanding of molecular mechanisms underlying addiction and uncover D2R-NMDAR heteromers as targets with potential therapeutic value.

scholarly journals The cue-reactivity paradigm: An ensemble of networks driving attention and cognition when viewing drug-related and natural-reward stimuli

2020 ◽  
Author(s):  
Lauren D. Hill-Bowen ◽  
Michael C. Riedel ◽  
Ranjita Poudel ◽  
Taylor Salo ◽  
Jessica S. Flannery ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Brain Activity ◽  
Cue Reactivity ◽  
Dorsal Striatum ◽  
Brain Regions ◽  
Reward Processing ◽  
Resting State Functional Connectivity ◽  
Addictive Disorders ◽  
Natural Reward ◽  
Elemental Nature

ABSTRACTBackgroundThe cue-reactivity paradigm is a widely adopted neuroimaging probe assessing brain activity linked to attention, memory, emotion, and reward processing associated with the presentation of appetitive stimuli. Lacking, is the apperception of more precise brain regions, neurocircuits, and mental operations comprising cue-reactivity’s multi-elemental nature. To resolve such complexities, we employed emergent meta-analytic techniques to enhance insight into drug and natural cue-reactivity in the brain.MethodsOperating from this perspective, we first conducted multiple coordinate-based meta-analyses to define common and distinct brain regions showing convergent activation across studies involving drug-related and natural-reward cue-reactivity paradigms. In addition, we examined the activation profiles of each convergent brain region linked to cue-reactivity as seeds in task-dependent and task-independent functional connectivity analyses. Using methods to cluster regions of interest, we categorized cue-reactivity into cliques, or sub-networks, based on the functional similarities between regions. Cliques were further classified with psychological constructs.ResultsWe identified a total of 164 peer-reviewed articles: 108 drug-related, and 56 natural-reward. When considering cue-reactivity collectively, across both drug and natural studies, activity convergence was observed in the dorsal striatum, limbic, insula, parietal, occipital, and temporal regions. Common convergent neural activity between drug and natural cue-reactivity was observed in the caudate, amygdala, thalamus, cingulate, and temporal regions. Drug distinct convergence was observed in the putamen, cingulate, and temporal regions, while natural distinct convergence was observed in the caudate, parietal, occipital, and frontal regions. We seeded identified cue-reactivity regions in meta-analytic connectivity modeling and resting-state functional connectivity analyses. Consensus hierarchical clustering of both connectivity analyses identified six distinct cliques that were further functionally characterized using the BrainMap and Neurosynth databases.ConclusionsWe examined the multifaceted nature of cue-reactivity and decomposed this construct into six elements of visual, executive function, sensorimotor, salience, emotion, and self-referential processing. Further, we demonstrated that these elements are supported by perceptual, sensorimotor, tripartite, and affective networks, which are essential to understanding the neural mechanisms involved in the development and or maintenance of addictive disorders.

Differential effects on natural reward processing in rats after repeated heroin

2013 ◽  
Vol 229 (1) ◽  
pp. 125-132 ◽  
Author(s):  
Ewa Galaj ◽  
Ivonne Cruz ◽  
Jordan Schachar ◽  
Matthew Koziolek ◽  
Robert Ranaldi
Keyword(s):  
Reward Processing ◽  
Differential Effects ◽  
Natural Reward

scholarly journals Natural Reward Experience Alters AMPA and NMDA Receptor Distribution and Function in the Nucleus Accumbens

PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e34700 ◽  
Author(s):  
Kyle K. Pitchers ◽  
Susanne Schmid ◽  
Andrea R. Di Sebastiano ◽  
Xu Wang ◽  
Steven R. Laviolette ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Nmda Receptor ◽  
Natural Reward ◽  
And Function ◽  
Receptor Distribution

Effects of Monetary Incentives on Task Switching

2012 ◽  
Vol 59 (4) ◽  
pp. 216-226 ◽  
Author(s):  
Thomas Kleinsorge ◽  
Gerhard Rinkenauer
Keyword(s):  
Task Switching ◽  
Temporal Dynamics ◽  
Reward Processing ◽  
General Level ◽  
Monetary Incentives ◽  
Switch Costs ◽  
Expectancy Effect ◽  
Reward Expectancy ◽  
Trial Basis

In two experiments, effects of incentives on task switching were investigated. Incentives were provided as a monetary bonus. In both experiments, the availability of a bonus varied on a trial-to-trial basis. The main difference between the experiments relates to the association of incentives to individual tasks. In Experiment 1, the association of incentives to individual tasks was fixed. Under these conditions, the effect of incentives was largely due to reward expectancy. Switch costs were reduced to statistical insignificance. This was true even with the task that was not associated with a bonus. In Experiment 2, there was a variable association of incentives to individual tasks. Under these conditions, the reward expectancy effect was bound to conditions with a well-established bonus-task association. In conditions in which the bonus-task association was not established in advance, enhanced performance of the bonus task was accompanied by performance decrements with the task that was not associated with a bonus. Reward expectancy affected mainly the general level of performance. The outcome of this study may also inform recently suggested neurobiological accounts about the temporal dynamics of reward processing.

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