ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2019
D1 receptor hypersensitivity in mice with low striatal D2 receptors facilitates select cocaine behaviors.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- Indirect Striatal Projection Neurons Drive a D2 Receptor-Dependent Pathway to Dyskinesia and Dystonia.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- PDE4 inhibitor rolipram dynamically regulates the balance between D1-MSNs and D2-MSNs in the DMS to modulate abnormal "Go" behavior associated with alcohol addiction.Acta pharmacologica Sinica · 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
- D2 autoreceptors gate vulnerability to cocaine use disorder.bioRxiv : the preprint server for biology · 2026Article
- A Cocaine-Activated Ensemble Exerts Increased Control Over Behavior While Decreasing in Size.Biological psychiatry · 2025Article
- Mu opioid receptors expressed in striatal D2 medium spiny neurons have divergent contributions to cocaine and morphine reward.Neuroscience · 2025Article
- Preexisting risk-avoidance and enhanced alcohol relief are driven by imbalance of the striatal dopamine receptors in mice.Nature communications · 2024Article
- Article
- A non-canonical striatopallidal Go pathway that supports motor control.Nature communications · 2023Article
- Low Dopamine D2 Receptor Expression Drives Gene Networks Related to GABA, cAMP, Growth and Neuroinflammation in Striatal Indirect Pathway Neurons.Biological psychiatry global open science · 2023Article
- Sleep Deprivation Induces Dopamine System Maladaptation and Escalated Corticotrophin-Releasing Factor Signaling in Adolescent Mice.Molecular neurobiology · 2023Article
- A non-canonical striatopallidal "Go" pathway that supports motor control.Research square · 2023Article
- The D1/D2-like receptor antagonist flupentixol and the D2-like receptor antagonist L-741626 decrease operant responding for nicotine and food and locomotor activity in male and female rats.Journal of psychopharmacology (Oxford, England) · 2023Article
- Article
- Dopamine D2 receptors bidirectionally regulate striatal enkephalin expression: Implications for cocaine reward.Cell reports · 2022Article
- The Modification of Offspring Stress-Related Behavior and the Expression ofInternational journal of molecular sciences · 2022Article
- Computational approaches to predicting treatment response to obesity using neuroimaging.Reviews in endocrine & metabolic disorders · 2022Review
- Downregulation of CDK5 signaling in the dorsal striatum alters striatal microcircuits implicating the association of pathologies with circadian behavior in mice.Molecular brain · 2022Article
- How changes in dopamine D2 receptor levels alter striatal circuit function and motivation.Molecular psychiatry · 2022Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Vulnerability for cocaine abuse in humans is associated with low dopamine D2 receptor (D2R) availability in the striatum. The mechanisms driving this vulnerability are poorly understood. In this study, we found that downregulating D2R expression selectively in striatal indirect-pathway neurons triggers a multitude of changes in D1 receptor (D1R)-expressing direct-pathway neurons, which comprise the other main subpopulation of striatal projection neurons. These changes include a leftward shift in the dose-response to a D1-like agonist that indicates a behavioral D1R hypersensitivity, a shift from PKA to ERK intracellular signaling cascades upon D1R activation, and a reduction in the density of bridging collaterals from D1R-expressing neurons to pallidal areas. We hypothesize that the D1R hypersensitivity underlies abuse vulnerability by facilitating the behavioral responses to repeated cocaine, such as locomotor sensitization and drug self-administration. We found evidence that littermate control mice develop D1R hypersensitivity after they are sensitized to cocaine. Indeed, D1-like agonist and cocaine cross-sensitize in control littermates and this effect was potentiated in mice lacking striatal D2Rs from indirect-pathway neurons. To our surprise, mice with low striatal D2Rs acquired cocaine self-administration similarly to littermate controls and showed no significant change in motivation to take cocaine but lower seeking. These findings indicate that downregulation of striatal D2Rs triggers D1R hypersensitivity to facilitate cocaine locomotor sensitization, which by itself was not associated with greater cocaine taking or seeking under the conditions tested.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.