ArticlePsychopharmacology2015
Effects of central activation of serotonin 5-HT2A/2C or dopamine D 2/3 receptors on the acute and repeated effects of clozapine in the conditioned avoidance response test.
Article in Psychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 18 citations in OpenAlex.
- "Intranasal clozapine sol-gel formulation induces an antipsychotic effect at a fraction of a comparable oral therapeutic dose".Translational psychiatry · 2026Article
- Continuous oral olanzapine or clozapine treatment initiated in adolescence has differential short- and long-term impacts on antipsychotic sensitivity than those initiated in adulthood.European journal of pharmacology · 2024Article
- The Nitric Oxide (NO) Donor Molsidomine Counteract Social Withdrawal and Cognition Deficits Induced by Blockade of the NMDA Receptor in the Rat.International journal of molecular sciences · 2023Article
- Article
- Synthesis and biological evaluation of a new class of multi-target heterocycle piperazine derivatives as potential antipsychotics.RSC advances · 2021Article
- Activation of 5-HTNeuropharmacology · 2018Article
- Behavioral, pharmacological and neuroanatomical analysis of serotonin 2C receptor agonism on maternal behavior in rats.Psychoneuroendocrinology · 2016Article
- Antipsychotic-induced sensitization and tolerance: Behavioral characteristics, developmental impacts, and neurobiological mechanisms.Journal of psychopharmacology (Oxford, England) · 2016Review
- GLP-1 receptor agonist exenatide restores atypical antipsychotic clozapine treatment-associated glucose dysregulation and damage of pancreatic islet beta cells in mice.Toxicology reports · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
rationaleAcute administration of clozapine (a gold standard of atypical antipsychotics) disrupts avoidance response in rodents, while repeated administration often causes a tolerance effect.
objectiveThe present study investigated the neuroanatomical basis and receptor mechanisms of acute and repeated effects of clozapine treatment in the conditioned avoidance response test in male Sprague-Dawley rats.
methods2,5-dimethoxy-4-iodo-amphetamine (DOI, a preferential 5-HT2A/2C agonist) or quinpirole (a preferential dopamine D2/3 agonist) was microinjected into the medial prefrontal cortex (mPFC) or nucleus accumbens shell (NAs), and their effects on the acute and long-term avoidance disruptive effect of clozapine were tested.
resultsIntra-mPFC microinjection of quinpirole enhanced the acute avoidance disruptive effect of clozapine (10 mg/kg, sc), while DOI microinjections reduced it marginally. Repeated administration of clozapine (10 mg/kg, sc) daily for 5 days caused a progressive decrease in its inhibition of avoidance responding, indicating tolerance development. Intra-mPFC microinjection of DOI at 25.0 (but not 5.0) μg/side during this period completely abolished the expression of clozapine tolerance. This was indicated by the finding that clozapine-treated rats centrally infused with 25.0 μg/side DOI did not show higher levels of avoidance responses than the vehicle-treated rats in the clozapine challenge test. Microinjection of DOI into the mPFC immediately before the challenge test also decreased the expression of clozapine tolerance.
conclusionsAcute behavioral effect of clozapine can be enhanced by activation of the D2/3 receptors in the mPFC. Clozapine tolerance expression relies on the neuroplasticity initiated by its antagonist action against 5-HT2A/2C receptors in the mPFC.
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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.