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• W2890924215 abstract "Serotonin 5-HT2A and metabotropic glutamate 2 (mGlu2) are neurotransmitter G protein-coupled receptors (GPCRs) involved in the signaling mechanisms underlying psychosis and schizophrenia treatment. Previous findings in mGlu2 knockout (KO) mice suggested that mGlu2 is necessary for head-twitch behavior, a rodent phenotype characteristic of hallucinogenic 5-HT2A receptor agonists. However, the role of mGlu2 in the behavioral effects induced by antipsychotic drugs remains poorly understood. Here, we tested antipsychotic-like behavioral phenotypes induced by the atypical antipsychotic clozapine in mGlu2-KO mice and wild-type control littermates. Locomotor activity was tested in mGlu2-KO mice and control littermates injected (i.p.) with clozapine (1.5 mg/kg) or vehicle followed by MK801 (0.5 mg/kg), PCP (7.5 mg/kg), amphetamine (6 mg/kg), scopolamine (2 mg/kg), or vehicle. Using a virally (HSV) mediated transgene expression approach, the role of frontal cortex mGlu2 in the modulation of MK801-induced locomotor activity by clozapine treatment was also evaluated. The effect of clozapine on hyperlocomotor activity induced by the dissociative drugs MK801 and phencyclidine (PCP) was decreased in mGlu2-KO mice as compared to controls. Clozapine treatment, however, reduced hyperlocomotor activity induced by the stimulant drug amphetamine and the deliriant drug scopolamine in both wild-type and mGlu2-KO mice. Virally mediated over-expression of mGlu2 in the frontal cortex of mGlu2-KO mice rescued the ability of clozapine to reduce MK801-induced hyperlocomotion. These findings further support the existence of a functionally relevant crosstalk between 5-HT2A and mGlu2 receptors in different preclinical models of antipsychotic activity." @default.
• W2890924215 created "2018-09-27" @default.
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• W2890924215 date "2018-09-12" @default.
• W2890924215 modified "2023-10-14" @default.
• W2890924215 title "Role of mGlu2 in the 5-HT2A receptor-dependent antipsychotic activity of clozapine in mice" @default.
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• W2890924215 doi "https://doi.org/10.1007/s00213-018-5015-4" @default.
• W2890924215 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6408231" @default.
• W2890924215 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30209534" @default.
• W2890924215 hasPublicationYear "2018" @default.
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