Back to Search
Start Over
Neurochemical and behavioral studies on the 5-HT 1A -dependent antipsychotic action of the mGlu 4 receptor agonist LSP4-2022.
- Source :
-
Neuropharmacology [Neuropharmacology] 2017 Mar 15; Vol. 115, pp. 149-165. Date of Electronic Publication: 2016 Jul 25. - Publication Year :
- 2017
-
Abstract
- LSP4-2022 is a novel, orthosteric agonist of mGlu <subscript>4</subscript> receptor that induces antipsychotic-like activity in animal studies. In the present study, the involvement of 5-HT <subscript>1A</subscript> receptors in LSP4-2022-induced antipsychotic actions and the neurochemical background of that interaction were investigated. In several behavioral tests the actions of effective doses of the compound (0.5-2 mg/kg) were antagonized via the administration of the 5-HT <subscript>1A</subscript> antagonist WAY100635 (0.1 mg/kg). The co-administration of sub-effective dose of the 5-HT <subscript>1A</subscript> agonist (R)-(S)-8-OH-DPAT (0.01 mg/kg) intensified the activity of ineffective doses of LSP4-2022, having no influence on the efficacy of the active doses. The co-administration of effective doses of both compounds did not intensify each other's action. In the microdialysis in vivo tests, MK-801 (0.6 mg/kg) induced an enhancement of the release of dopamine, serotonin, glutamate and GABA in the prefrontal cortex. Administration of LSP4-2022 (2 mg/kg) abolished this MK-801-induced effect on neurotransmitter release. Co-administration with WAY100635 (0.1 mg/kg), a 5-HT <subscript>1A</subscript> antagonist, completely (dopamine, serotonin) or partially (glutamate, GABA) counteracted this LSP4-2022-induced effect. Subsequently, the patch-clamp recordings of spontaneous EPSCs were performed. sEPSCs were evoked in slices from the mouse prefrontal cortex by DOI (10 μM). LSP4-2022 (2.5; 5 and 10 μm) reversed DOI-induced changes in both the frequency and amplitude of the sEPSCs, but the more robust effect on the frequency was observed. The administration of WAY100635 had no effect on the LSP4-2022-induced effects on sEPSCs, indicating that the mGlu <subscript>4</subscript> -5-HT <subscript>1A</subscript> interaction does not occur via single-neuron signaling but involves neuronal circuits that regulate neurotransmitter release. This article is part of the Special Issue entitled 'Metabotropic Glutamate Receptors, 5 years on'.<br /> (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Dizocilpine Maleate pharmacology
Dose-Response Relationship, Drug
Excitatory Amino Acid Agonists pharmacology
Interpersonal Relations
Locomotion drug effects
Male
Mice
Piperazines pharmacology
Pyridines pharmacology
Rats
Rats, Wistar
Serotonin Antagonists pharmacology
Antipsychotic Agents pharmacology
Locomotion physiology
Phosphinic Acids pharmacology
Receptor, Serotonin, 5-HT1A physiology
Receptors, Metabotropic Glutamate agonists
Receptors, Metabotropic Glutamate physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7064
- Volume :
- 115
- Database :
- MEDLINE
- Journal :
- Neuropharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 27465045
- Full Text :
- https://doi.org/10.1016/j.neuropharm.2016.06.025