ArticleSchizophrenia bulletin2014
Prior antipsychotic drug treatment prevents response to novel antipsychotic agent in the methylazoxymethanol acetate model of schizophrenia.
Article in Schizophrenia bulletin, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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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
38 citing papers in PubMed, 73 citations in OpenAlex.
- Effects of diazepam on hippocampal blood flow in people at clinical high risk for psychosis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Trial
- Glyceryl trinitrate in first-episode psychosis unmedicated with antipsychotics: A randomised controlled pilot study.Journal of psychopharmacology (Oxford, England) · 2020Trial
- Toward a Pluralistic Model for the Schizophrenia Spectrum-Dopamine and Beyond.JAMA psychiatry · 2026Review
- Animal Models for Drug Discovery in Schizophrenia: A Critical View from a Clinical Perspective.Pharmaceutical medicine · 2026Review
- Antipsychotic Drug Action, Novel Treatment Targets, and the Failure of Current Clinical Trial Designs in Evaluating New Target Molecules.Biological psychiatry · 2026Review
- Novel positive allosteric modulators of alpha 5 subunit-containing GABASchizophrenia research · 2026Article
- Effects of Benzodiazepine Exposure on Real-World Clinical Outcomes in Individuals at Clinical High Risk for Psychosis.Schizophrenia bulletin · 2025Observational
- Corticolimbic circuitry as a druggable target in schizophrenia spectrum disorders: a narrative review.Translational psychiatry · 2025Review
- Synaptotagmin-11 deficiency mediates schizophrenia-like behaviors in mice via dopamine over-transmission.Nature communications · 2024Article
- Prenatal Exposure to MAM Impairs mPFC and Hippocampal Inhibitory Function in Mice during Adolescence and Adulthood.eNeuro · 2024Article
- The excitatory-inhibitory balance as a target for the development of novel drugs to treat schizophrenia.Biochemical pharmacology · 2024Review
- Sex-dependent emergence of prepubertal social dysfunction and augmented dopamine activity in a neurodevelopmental rodent model relevant for schizophrenia.Schizophrenia research · 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
- Synthesis and Receptor Binding Studies of α5 GABAMolecules (Basel, Switzerland) · 2023Article
- Hippocampal circuit dysfunction in psychosis.Translational psychiatry · 2022Review
- Treatment-resistant schizophrenia: How far have we traveled?Frontiers in psychiatry · 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
- Nicotine Administration Normalizes Behavioral and Neurophysiological Perturbations in the MAM Rodent Model of Schizophrenia.The international journal of neuropsychopharmacology · 2021Article
- Peripubertal mGluR2/3 Agonist Treatment Prevents Hippocampal Dysfunction and Dopamine System Hyperactivity in Adulthood in MAM Model of Schizophrenia.Schizophrenia bulletin · 2021Article
- Beyond Dopamine Receptor Antagonism: New Targets for Schizophrenia Treatment and Prevention.International journal of molecular sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Trials of novel compounds for the treatment of schizophrenia are typically tested in patients following brief withdrawal of ongoing medication despite known long-term changes in the dopamine (DA) system following chronic antipsychotic drug therapy. The present study explored the impact of withdrawal from repeated haloperidol (HAL) treatment, as well as the response to a novel α5 gamma-aminobutyric acid (GABA(A)) receptor positive allosteric modulator (α5PAM), on the activity of the DA system in the methylazoxymethanol acetate (MAM) neurodevelopmental model of schizophrenia. Electrophysiological recordings were conducted from DA neurons in the ventral tegmental area of MAM and saline (SAL) rats following 7-day withdrawal from repeated HAL (21 d, 0.6 mg/kg, orally). In separate animals, amphetamine-induced locomotion was measured to assess changes in DA behavioral sensitivity. SAL rats withdrawn from HAL demonstrated reduced spontaneous DA neuron activity along with an enhanced locomotor response to amphetamine, indicative of the development of DA supersensitivity. Both α5PAM treatment and ventral hippocampal (vHPC) inactivation reversed the DA neuron depolarization block following HAL withdrawal in SAL rats. In contrast, MAM rats withdrawn from HAL exhibited reduced spontaneous DA activity and enhanced locomotor response to amphetamine compared with untreated SAL rats; however, this condition was unresponsive to α5PAM treatment or vHPC inactivation. Withdrawal from prior HAL treatment interferes with the therapeutic actions of this novel treatment in the MAM model of schizophrenia. Consequently, testing novel compounds on chronically treated schizophrenia patients may be ineffective.
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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.