title: Pharmacological evaluation of the anxiolytic-like effects of EMD 386088, a partial 5-HT6 receptor agonist, in the rat elevated plus-maze and Vogel conflict tests.
abstract: The 5-HT6 is one of the most recent additions to the 5-HT receptor family. Its pharmacological profile and anatomical distribution is suggestive of a putative role in mood disorders. Most of preclinical evidence suggests an anxiolytic-like action of 5-HT6 receptor antagonists. Evaluation the anxiolytic-like effects of EMD 386088, a partial 5-HT6receptor agonist, and its putative mechanism of action in rats. EMD 386088, administered intraperitoneally at a dose of 2.5 mg/kg evoked specific anxiolytic-like activity in the automated version of the conflict drinking Vogel and the elevated plus-maze tests visible by increasing all parameters indicating a potential anti-anxiety effect. Its activity was blocked by the selective 5-HT6 receptor antagonist SB 271046, but not by the selective GABAA/benzodiazepine receptor antagonist flumazenil. EMD 386088 did not intensify an anxiolytic-like effect produced by diazepam in the elevated plus-maze test. These findings suggest that EMD 386088, a 5-HT6 receptor agonist, produces anxiolytic-like activity after systemic administration which may result from direct stimulation of 5-HT6 receptors.
authors.affiliation: Department of Clinical Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland. Electronic address: m.jastrzebska-wiesek@uj.edu.pl.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Jastrzębska-Więsek
authors.affiliation: Department of Pharmacobiology, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Siwek
authors.affiliation: Department of Clinical Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Partyka
authors.affiliation: Department of Pharmacodynamics, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Kubacka
authors.affiliation: Department of Pharmacodynamics, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland.
authors.forename: Szczepan
authors.initials: S
authors.lastname: Mogilski
authors.affiliation: Department of Clinical Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Wasik
authors.affiliation: Department of Pharmaceutical Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland; Adamed Ltd., Pienków 149, Czosnów k/Warszawy, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Kołaczkowski
authors.affiliation: Department of Clinical Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Wesołowska
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy* / Q000503:physiopathology; D003220:Conflict, Psychological; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects / Q000502:physiology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009483:Neuropsychological Tests; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology*; D011897:Random Allocation; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
chemical_list: C534240:5-chloro-2-methyl-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole; D014151:Anti-Anxiety Agents; D007211:Indoles; D011725:Pyridines; D011963:Receptors, GABA-A; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D017366:Serotonin Receptor Agonists; C097216:serotonin 6 receptor
keywords: 5-HT(3) functional assay in vitro; 5-HT(6) receptor; Anxiety; Conflict drinking test; EMD 386088; Elevated plus-maze test; Rats; SB 271046