Rationale: Metabotropic glutamate receptors and muscarinic M receptors have been proposed as novel targets for various brain disorders, including schizophrenia. Both receptors are coupled to G proteins and are expressed in brain circuits that are important in schizophrenia. Therefore, their mutual activation may be an effective treatment and allow minimizing the doses of ligands required for optimal activity.
Objectives: In the present studies, subactive doses of mGlu and M activators (LSP4-2022 and VU152100, respectively) were administered to investigate the mutual interaction between mGlu and M receptors in animal models of schizophrenia.
Methods: The behavioral tests used were MK-801-induced hyperactivity, (±)-2.5-dimethoxy-4-iodoamphetamine hydrochloride (DOI)-induced head twitches, the modified forced swim test, and MK-801-induced disruptions of social interactions and novel object recognition. DOI-induced spontaneous excitatory postsynaptic currents (sEPSCs) in brain slices and positron emission tomography (PET) in were used to establish the ability of these compounds to modulate the glutamatergic and dopaminergic systems. Rotarod was used to assess putative adverse effects.
Results: The mutual administration of subactive doses of LSP4-2022 and VU152100 exerted similar antipsychotic-like efficacy in animals as observed for active doses of both compounds, indicating their additive actions. VU152100 inhibited the DOI-induced frequency (but not amplitude) of sEPSCs in the frontal cortex, confirming presynaptic regulation of glutamate release. Both compounds reversed amphetamine-induced decrease in D receptor levels in the striatum, as measured with [F]fallypride. The compounds did not induce any motor impartments when measured in rotarod test.
Conclusions: Based on our results, the simultaneous activation of M and mGlu receptors is beneficial in reversing MK-801- and amphetamine-induced schizophrenia-related changes in animals.
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http://dx.doi.org/10.1007/s00213-018-4980-y | DOI Listing |
Clin Teach
February 2025
Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
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Department of Psychology, University of Milano-Bicocca and Milan Center for Neuroscience, Milan, Italy.
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View Article and Find Full Text PDFAnim Microbiome
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The composition and function of animal gut microbiota are shaped by various factors, among which diet is one of the major factors. Diet is affected by seasonal shifts and geographical differences, which in turn impact the host's nutritional levels. To adapt to these environmental changes, the gut microbiome often produces matching responses.
View Article and Find Full Text PDFJ Nanobiotechnology
December 2024
Henan Key Laboratory of Nanocomposite and Applications, Institute of Nanostructured Functional Materials, Huanghe Science and Technology College, Zhengzhou, 450006, Henan, China.
Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease which is closely related with the overproduced reactive oxygen species (ROS), increased pro-inflammatory cytokines and disordered intestinal microbes. However, current therapeutic methods usually ignored the interrelation among the pathogenesis, and mainly focused on a single factor, inducing clinical outcomes unsatisfied. Herein, biocompatible infinite coordination polymers of drugs (Ce-SASP-RS ICPs) composed of Ce ions, FDA-approved drug sulfasalazine (SASP) and natural ingredient resistant starch (RS) were developed for synergistic treatment of IBD.
View Article and Find Full Text PDFPrimates
December 2024
Université de Strasbourg, IPHC, UMR7178, CNRS, Strasbourg, France.
Interspecies interactions present diverse forms and functions, contributing significantly to ecological and social dynamics. This study focuses on the mounting behaviours of Japanese macaques (Macaca fuscata) towards Sika deer (Cervus nippon), a rare and still unexplained phenomenon, with minimal emphasis on the behaviour of the deer. Using video data from two distinct sites, Yakushima and Minoh, Japan, we documented 45 sequences of macaque-deer interactions and analysed macaques' behaviours and deer behaviours using focal and behavioural sampling techniques.
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