ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Antipsychotic drugs rapidly induce dopamine neuron depolarization block in a developmental rat model of schizophrenia.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 121 citations in OpenAlex.
- Antipsychotic Drug Action, Novel Treatment Targets, and the Failure of Current Clinical Trial Designs in Evaluating New Target Molecules.Biological psychiatry · 2026Review
- Lost in translation: why don't dopamine D2 antagonists cure addictions?Journal of psychiatry & neuroscience : JPN · 2026Article
- Spatial and functional profiles distinguish target sets of Parkinson's disease and antipsychotic drugs with different clinical effects.Translational psychiatry · 2025Article
- An Emerging Prospective of Antipsychotics for Treating Neurodegenerative Disorders.Current pharmaceutical design · 2025Review
- Plasticity of ventral tegmental area disturbance during abstinence after repeated amphetamine exposure: restoration by selective activation of group II metabotropic glutamate receptors.Frontiers in pharmacology · 2025Article
- Functional properties of corticothalamic circuits targeting paraventricular thalamic neurons.Neuron · 2024Article
- Current Findings and Potential Mechanisms of KarXT (Xanomeline-Trospium) in Schizophrenia Treatment.Clinical drug investigation · 2024Review
- Normative modelling of molecular-based functional circuits captures clinical heterogeneity transdiagnostically in psychiatric patients.Communications biology · 2024Article
- The antipsychotic agent sulpiride microinjected into the ventral pallidum restores positive symptom-like habituation disturbance in MAM-E17 schizophrenia model rats.Scientific reports · 2024Article
- Sex-dependent emergence of prepubertal social dysfunction and augmented dopamine activity in a neurodevelopmental rodent model relevant for schizophrenia.Schizophrenia research · 2023Article
- Deficiency of Cullin 3, a Protein Encoded by a Schizophrenia and Autism Risk Gene, Impairs Behaviors by Enhancing the Excitability of Ventral Tegmental Area (VTA) DA Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Insights into the Mechanism of Action of Antipsychotic Drugs Derived from Animal Models: Standard of Care versus Novel Targets.International journal of molecular sciences · 2023Review
- Blocking D2/D3 dopamine receptors in male participants increases volatility of beliefs when learning to trust others.Nature communications · 2023Article
- Dopamine Dynamics and Neurobiology of Non-Response to Antipsychotics, Relevance for Treatment Resistant Schizophrenia: A Systematic Review and Critical Appraisal.Biomedicines · 2023Review
- Influence of the Co-Adsorbed Ions on the Surface-Enhanced Raman Scattering Spectra of Dopamine Adsorbed on Nanostructured Silver.Materials (Basel, Switzerland) · 2022Article
- Article
- Dopaminergic dysfunction and excitatory/inhibitory imbalance in treatment-resistant schizophrenia and novel neuromodulatory treatment.Molecular psychiatry · 2022Review
- Adult stress exposure blunts dopamine system hyperresponsivity in a neurodevelopmental rodent model of schizophrenia.Schizophrenia (Heidelberg, Germany) · 2022Article
- Using animal models for the studies of schizophrenia and depression: The value of translational models for treatment and prevention.Frontiers in behavioral neuroscience · 2022Review
- Early Pup Removal Leads to Social Dysfunction and Dopamine Deficit in Late Postpartum Rats: Prevention by Social Support.Frontiers in global women's health · 2021Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
Repeated administration of antipsychotic drugs to normal rats has been shown to induce a state of dopamine neuron inactivation known as depolarization block, which correlates with the ability of the drugs to exhibit antipsychotic efficacy and extrapyramidal side effects in schizophrenia patients. Nonetheless, in normal rats depolarization block requires weeks of antipsychotic drug administration, whereas schizophrenia patients exhibit initial effects soon after initiating antipsychotic drug treatment. We now report that, in a developmental disruption rat model of schizophrenia [methyl-azoxymethanol acetate (20 mg/kg, i.p.) injected into G17 pregnant female rats, with offspring tested as adults], the extant hyperdopaminergic state combines with the excitatory actions of a first- (haloperidol; 0.6 mg/kg, i.p.) and a second- (sertindole; 2.5 mg/kg, i.p.) generation antipsychotic drug to rapidly induce depolarization block in ventral tegmental area dopamine neurons. Acute injection of either antipsychotic drug induced an immediate reduction in the number of spontaneously active dopamine neurons (cells per electrode track; termed population activity). Repeated administration of either antipsychotic drug for 1, 3, 7, 15, and 21 d continued to reduce dopamine neuron population activity. Both acute and repeated effects on population activity were reversed by acute apomorphine injections, which is consistent with the reversal of dopamine neuron depolarization block. Although this action may account for the effects of D2 antagonist drugs on alleviating psychosis and the lack of development of tolerance in humans, the drugs appear to do so by inducing an offsetting deficit rather than attacking the primary pathology present in schizophrenia.
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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.