Increased vulnerability to cocaine in mice lacking dopamine D3 receptors.
paper
Cited
Public
Unavailable
- Authors
- Song, Rui; Zhang, Hai-Ying; Li, Xia; Bi, Guo-Hua; Gardner, Eliot L; Xi, Zheng-Xiong
- Year
- 2012
- Journal
- Proceedings of the National Academy of Sciences of the United States of America
- PMID
- 23045656
- DOI
- 10.1073/pnas.1205297109
- PMCID
- PMC3491487
Neuroimaging studies using positron emission tomography suggest that reduced dopamine D(2) receptor availability in the neostriatum is associated with increased vulnerability to drug addiction in humans and experimental animals. The role of D(3) receptors (D(3)Rs) in the neurobiology of addiction remains unclear, however. Here we report that D(3)R KO (D(3)(-/-)) mice display enhanced cocaine self-administration and enhanced motivation for cocaine-taking and cocaine-seeking behavior. This increased vulnerability to cocaine is accompanied by decreased dopamine response to cocaine secondary to increased basal levels of extracellular dopamine in the nucleus accumbens, suggesting a compensatory response to decreased cocaine reward in D(3)(-/-) mice. In addition, D(3)(-/-) mice also display up-regulation of dopamine transporters in the striatum, suggesting a neuroadaptative attempt to normalize elevated basal extracellular dopamine. These findings suggest that D(3)R deletion increases vulnerability to cocaine, and that reduced D(3)R availability in the brain may constitute a risk factor for the development of cocaine addiction.
No figures extracted from this document.
No chunks β full text not yet ingested.
No entities extracted from this document yet.
No uploaded files.
Not in any collection.
No citations found.
In this knowledge base
| Title | Year | PMID |
|---|---|---|
| The genetic epidemiology of substance use disorder: A review. | 2017 | 28938182 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Cocaine-Induced Immediate-Early Gene Expression in the Nucleus Accumbens: Roles of Separate cAMP Sensors. | Zhang HY et al. | β | 2026 | β |
| Dopamine D2 receptor modulation of insulin receptor signaling in the central amygdala: implications for compulsive-like eating behavior. | Kim B et al. | β | 2026 | β |
| Vitamin A deficiency induces sex-specific reward processing alterations through a dysregulation of the mesolimbic dopamine transmission in mice. | Couty P et al. | β | 2026 | β |
| Developmental vitamin A deficiency induces sex-specific reward processing alterations through a dysregulation of the mesolimbic dopamine transmission in mice | Couty P et al. | β | 2025 | β |
| Dissociable control of motivation and reinforcement by distinct ventral striatal dopamine receptors. | Enriquez-Traba J et al. | β | 2025 | β |
| Dopamine D3 receptor in the nucleus accumbens modulates opioid taking and seeking in mice. | Yang MD et al. | β | 2025 | β |
| Exploring Genetic and Receptor-Based Dopaminergic Strategies for Antidepressant Drug Development. | Pannu A et al. | β | 2025 | β |
| Higher levels of D2R and D3R in the frontal-striatal regions are associated with reduced perseverative reward seeking after opioid abstinence. | Li Y et al. | β | 2025 | β |
| Presynaptic and Postsynaptic Mesolimbic Dopamine D<sub>3</sub> Receptors Play Distinct Roles in Cocaine Versus Opioid Reward in Mice. | Xi ZX et al. | β | 2024 | β |
| cAMP-mediated upregulation of HCN channels in VTA dopamine neurons promotes cocaine reinforcement. | Mu L et al. | β | 2023 | β |
| The influence of dopamine autoreceptors on temperament and addiction risk. | Zald DH | β | 2023 | β |
| Therapeutic Potential of Dopamine and Related Drugs as Anti-Inflammatories and Antioxidants in Neuronal and Non-Neuronal Pathologies. | Bandala C et al. | β | 2023 | β |
| Activation of mesocorticolimbic dopamine projections initiates cue-induced reinstatement of reward seeking in mice. | Jing MY et al. | β | 2022 | β |
| Aquaporin-4 deletion attenuates opioid-induced addictive behaviours associated with dopamine levels in nucleus accumbens. | Lv Y et al. | β | 2022 | β |
| Repeated cocaine administration upregulates CB<sub>2</sub> receptor expression in striatal medium-spiny neurons that express dopamine D<sub>1</sub> receptors in mice. | Zhang HY et al. | β | 2022 | β |
| The dopamine transporter gene SLC6A3: multidisease risks. | Reith MEA et al. | β | 2022 | β |
| Cannabidiol prevents several of the behavioral alterations related to cocaine addiction in mice. | Ledesma JC et al. | β | 2021 | β |
| Cell-Type-Specific Adaptions in Striatal Medium-Sized Spiny Neurons and Their Roles in Behavioral Responses to Drugs of Abuse. | Allichon MC et al. | β | 2021 | β |
| Deletion of VGLUT2 in midbrain dopamine neurons attenuates dopamine and glutamate responses to methamphetamine in mice. | Shen H et al. | β | 2021 | β |
| Identification of the Risk Genes Associated With Vulnerability to Addiction: Major Findings From Transgenic Animals. | Jordan CJ et al. | β | 2021 | β |
| Is It Possible to Shift from Down to Top Rank? A Focus on the Mesolimbic Dopaminergic System and Cocaine Abuse. | Amaral IM et al. | β | 2021 | β |
| Pharmacokinetic and pharmacodynamic analyses of cocaine and its metabolites in behaviorally divergent inbred mouse strains. | Zhu J et al. | β | 2021 | β |
| The changing opioid crisis: development, challenges and opportunities. | Volkow ND et al. | β | 2021 | β |
| Dopamine D3 receptor-based medication development for the treatment of opioid use disorder: Rationale, progress, and challenges. | Galaj E et al. | β | 2020 | β |
| Negative Symptoms of Schizophrenia and Dopaminergic Transmission: Translational Models and Perspectives Opened by iPSC Techniques. | Collo G et al. | β | 2020 | β |
| (Β±)VK4-40, a novel dopamine D<sub>3</sub> receptor partial agonist, attenuates cocaine reward and relapse in rodents. | Jordan CJ et al. | β | 2020 | β |
| Disentangling the diverse roles of dopamine D2 receptors in striatal function and behavior. | Gallo EF | β | 2019 | β |
| Selective D<sub>2</sub> and D<sub>3</sub> receptor antagonists oppositely modulate cocaine responses in mice via distinct postsynaptic mechanisms in nucleus accumbens. | Manvich DF et al. | β | 2019 | β |
| Selective dopamine D3 receptor antagonist YQA14 inhibits morphine-induced behavioral sensitization in wild type, but not in dopamine D3 receptor knockout mice. | Lv Y et al. | β | 2019 | β |
| The role of prefrontal cortex dopamine D2 and D3 receptors in the mechanism of action of venlafaxine and deep brain stimulation in animal models of treatment-responsive and treatment-resistant depression. | Papp M et al. | β | 2019 | β |
| Deletion of the type 2 metabotropic glutamate receptor increases heroin abuse vulnerability in transgenic rats. | Gao JT et al. | β | 2018 | β |
| Dopamine D1 and D3 receptor polypharmacology as a potential treatment approach for substance use disorder. | Galaj E et al. | β | 2018 | β |
| Genetic deletion of the dopamine D3 receptor increases vulnerability to heroin in mice. | Zhan J et al. | β | 2018 | β |
| Genetic deletion of vesicular glutamate transporter in dopamine neurons increases vulnerability to MPTP-induced neurotoxicity in mice. | Shen H et al. | β | 2018 | β |
| Increased Alcohol Seeking in Mice Lacking Gpr88 Involves Dysfunctional Mesocorticolimbic Networks. | Ben Hamida S et al. | β | 2018 | β |
| mGluR5 antagonism inhibits cocaine reinforcement and relapse by elevation of extracellular glutamate in the nucleus accumbens via a CB1 receptor mechanism. | Li X et al. | β | 2018 | β |
| Role of dopamine D3 receptor in alleviating behavioural deficits in animal models of post-traumatic stress disorder. | Song D et al. | β | 2018 | β |
| Deletion of Type 2 Metabotropic Glutamate Receptor Decreases Sensitivity to Cocaine Reward in Rats. | Yang HJ et al. | β | 2017 | β |
| Dopaminergic mechanisms in memory consolidation and antidepressant reversal of a chronic mild stress-induced cognitive impairment`. | Papp M et al. | β | 2017 | β |
| The dopamine D3 receptor, a quarter century later. | Sokoloff P et al. | β | 2017 | β |
| The genetic epidemiology of substance use disorder: A review. | Prom-Wormley EC et al. | β | 2017 | β |
| The novel dopamine D3 receptor antagonists/partial agonists CAB2-015 and BAK4-54 inhibit oxycodone-taking and oxycodone-seeking behavior in rats. | You ZB et al. | β | 2017 | β |
| The Role of Working Memory for Cognitive Control in Anorexia Nervosa versus Substance Use Disorder. | Brooks SJ et al. | β | 2017 | β |
| Aggregated single-walled carbon nanotubes attenuate the behavioural and neurochemical effects of methamphetamine in mice. | Xue X et al. | β | 2016 | β |
| A selective D3 receptor antagonist YQA14 attenuates methamphetamine-induced behavioral sensitization and conditioned place preference in mice. | Sun L et al. | β | 2016 | β |
| Dopamine D3 Receptor Availability Is Associated with Inflexible Decision Making. | Groman SM et al. | β | 2016 | β |
| Epigenetics and addiction. | Cadet JL et al. | β | 2016 | β |
| T394A Mutation at the ΞΌ Opioid Receptor Blocks Opioid Tolerance and Increases Vulnerability to Heroin Self-Administration in Mice. | Wang XF et al. | β | 2016 | β |
| Dopamine D3 receptor-dependent changes in alpha6 GABAA subunit expression in striatum modulate anxiety-like behaviour: Responsiveness and tolerance to diazepam. | Leggio GM et al. | β | 2015 | β |
| Pharmacological modulation of abnormal involuntary DOI-induced head twitch response movements in male DBA/2J mice: II. Effects of D3 dopamine receptor selective compounds. | Rangel-Barajas C et al. | β | 2015 | β |
| Species differences in cannabinoid receptor 2 and receptor responses to cocaine self-administration in mice and rats. | Zhang HY et al. | β | 2015 | β |
| The Brain on Drugs: From Reward to Addiction. | Volkow ND et al. | β | 2015 | β |
| Addiction science: Uncovering neurobiological complexity. | Volkow ND et al. | β | 2014 | β |
| A novel dopamine D3 receptor antagonist YQA14 inhibits methamphetamine self-administration and relapse to drug-seeking behaviour in rats. | Chen Y et al. | β | 2014 | β |
| Blockade of D3 receptors by YQA14 inhibits cocaine's rewarding effects and relapse to drug-seeking behavior in rats. | Song R et al. | β | 2014 | β |
| Cannabinoid CB2 receptors modulate midbrain dopamine neuronal activity and dopamine-related behavior in mice. | Zhang HY et al. | β | 2014 | β |
| Dopamine D1 and D3 receptors mediate reconsolidation of cocaine memories in mouse models of drug self-administration. | Yan Y et al. | β | 2014 | β |
| Dopamine D3 and 5-HT1B receptor dysregulation as a result of psychostimulant intake and forced abstinence: Implications for medications development. | Neisewander JL et al. | β | 2014 | β |
| Dopamine D3 receptors in the basolateral amygdala and the lateral habenula modulate cue-induced reinstatement of nicotine seeking. | Khaled MA et al. | β | 2014 | β |
| Inhibitory modulation of CART peptides in accumbal neuron through decreasing interaction of CaMKIIΞ± with dopamine D3 receptors. | Cai Z et al. | β | 2014 | β |
| Dopamine D(3) receptor as a new pharmacological target for the treatment of depression. | Leggio GM et al. | β | 2013 | β |
| Dopamine D(3) receptor deletion or blockade attenuates cocaine-induced conditioned place preference in mice. | Song R et al. | β | 2013 | β |
| Dopamine D3 receptors regulate reconsolidation of cocaine memory. | Yan Y et al. | β | 2013 | β |
| Effects of saikosaponin A on cocaine self-administration in rats. | Yoon SS et al. | β | 2013 | β |
| Fast-scan cyclic voltammetry analysis of dynamic serotonin reponses to acute escitalopram. | Wood KM et al. | β | 2013 | β |
| Fenobam sulfate inhibits cocaine-taking and cocaine-seeking behavior in rats: implications for addiction treatment in humans. | Keck TM et al. | β | 2013 | β |
| Repeated toluene exposure increases c-Fos in catecholaminergic cells of the nucleus accumbens shell. | Tomaszycki ML et al. | β | 2013 | β |
| The dopamine D(3) receptor antagonist YQA14 that inhibits the expression and drug-prime reactivation of morphine-induced conditioned place preference in rats. | Hu R et al. | β | 2013 | β |
| The dopamine D<sub>3</sub> receptor antagonist YQA14 that inhibits the expression and drug-primed reactivation of morphine-induced conditioned place preference in rats. | Hu R et al. | β | 2013 | β |
| Neurogenetics and Nutrigenomics of Neuro-Nutrient Therapy for Reward Deficiency Syndrome (RDS): Clinical Ramifications as a Function of Molecular Neurobiological Mechanisms. | Blum K et al. | β | 2012 | β |