ArticleProceedings of the National Academy of Sciences of the United States of America2016
In vivo imaging identifies temporal signature of D1 and D2 medium spiny neurons in cocaine reward.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 225 papers.
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Who cites it
225 citing papers in PubMed, 349 citations in OpenAlex.
- Cell-type-specific disruption of nucleus accumbens social representations in a mouse model of autism.Neuron · 2026Article
- Synaptic Actions of Estradiol in the Brain's Reward System: Linking Mechanisms to Behavior and Disease.Biological psychiatry global open science · 2026Review
- Paternal epigenetic inheritance increases susceptibility to methamphetamine taking.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Transposable Elements Are Dynamically Regulated in Medium Spiny Neurons and May Contribute to the Molecular and Behavioral Adaptations to Cocaine.Biological psychiatry · 2026Article
- Learning dynamically regulates stimulus discrimination of ventral striatal D1 receptor expressing neurons.Science advances · 2026Article
- DRD1 and DRD2 dopamine-sensitive neurons in the central amygdala respond differently to rewarding and aversive stimuli.Translational psychiatry · 2026Article
- Review
- Nucleus accumbens medial shell D1 and D2 medium spiny neurons signal the valence of conditioned stimuli in a sex-dependent manner.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Inherited input and local transformations shape the spatiotemporal organization of pathway specific striatal signals for motivated behavior.bioRxiv : the preprint server for biology · 2026Article
- D3 dopamine receptors implicate a striatal neuronal subtype in the aversive effects of the antipsychotic drug quetiapine.bioRxiv : the preprint server for biology · 2026Article
- Unpredictable Chronic Mild Stress Upregulates Dopamine Receptor Expression Independent of Fatty Acid-Binding Protein 7 Gene Deletion.Neurochemical research · 2026Article
- Aberrantly integrated adult-born immature neurons disrupt brain-wide networks during spatial memory processing.Molecular psychiatry · 2026Article
- Remifentanil self-administration promotes circuit- and sex-specific adaptations within the prefrontal-accumbens pathways.bioRxiv : the preprint server for biology · 2026Article
- Postnatal reduction of eIF4E overexpression in D1-SPNs ameliorates KCNQ channel dysfunction, hyperexcitability and ASD-like behaviours.Cellular and molecular life sciences : CMLS · 2026Article
- Stress-responsive nucleus accumbens dopamine D2 receptor-expressing neurons modulate cocaine-induced behavioral sensitization.Frontiers in cellular neuroscience · 2026Article
- Projection-specific roles of basolateral amygdala Thy1 neurons in alcohol-induced place preference.Molecular psychiatry · 2026Article
- Remifentanil self-administration promotes circuit- and sex-specific adaptations within the prefrontal-accumbens pathways.Frontiers in cellular neuroscience · 2026Article
- Astrocytic CREB regulates transcriptomic, neuronal, and behavioral responses to cocaine.Science advances · 2025Article
- Corticostriatal cocaine-seeking ensembles are defined by differing gene expression from sucrose-seeking ensembles using a within-subject dual self-administration and seeking mouse model.Addiction neuroscience · 2025Article
- A Drd1-cre mouse line with nucleus accumbens gene dysregulation exhibits blunted fentanyl seeking.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
165 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
The reinforcing and rewarding properties of cocaine are attributed to its ability to increase dopaminergic transmission in nucleus accumbens (NAc). This action reinforces drug taking and seeking and leads to potent and long-lasting associations between the rewarding effects of the drug and the cues associated with its availability. The inability to extinguish these associations is a key factor contributing to relapse. Dopamine produces these effects by controlling the activity of two subpopulations of NAc medium spiny neurons (MSNs) that are defined by their predominant expression of either dopamine D1 or D2 receptors. Previous work has demonstrated that optogenetically stimulating D1 MSNs promotes reward, whereas stimulating D2 MSNs produces aversion. However, we still lack a clear understanding of how the endogenous activity of these cell types is affected by cocaine and encodes information that drives drug-associated behaviors. Using fiber photometry calcium imaging we define D1 MSNs as the specific population of cells in NAc that encodes information about drug associations and elucidate the temporal profile with which D1 activity is increased to drive drug seeking in response to contextual cues. Chronic cocaine exposure dysregulates these D1 signals to both prevent extinction and facilitate reinstatement of drug seeking to drive relapse. Directly manipulating these D1 signals using designer receptors exclusively activated by designer drugs prevents contextual associations. Together, these data elucidate the responses of D1- and D2-type MSNs in NAc to acute cocaine and during the formation of context-reward associations and define how prior cocaine exposure selectively dysregulates D1 signaling to drive relapse.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.