title: Antidepressant-like activity of EMD 386088, a 5-HT6 receptor partial agonist, following systemic acute and chronic administration to rats.
abstract: The study was designed to examine the potency of EMD 386088, a 5-HT6 receptor partial agonist, to exert antidepressant-like properties in animal models following acute and chronic intraperitoneal administration to rats. The modified rat forced swim test (FST) was utilized to examine a potential antidepressant effect of EMD 386088 after acute treatment (30 min before the test) and three times in a 24-h administration scheme (24 h, 5 h, and 30 min prior to the FST). The olfactory bulbectomy (OB) model was used to assess its antidepressant-like properties after chronic treatment (the drug was administered once daily for 14 days). EMD 386088 showed an antidepressant-like effect in all conducted tests. Its activity in FST after its acute administration (5 mg/kg) was blocked by the selective 5-HT6 receptor antagonist SB 271046. The obtained results seem to be specific, as there was no observed locomotor stimulation by the drug given at a lower/antidepressant dose. In the three times in the 24-h treatment scheme, EMD 386088 (2.5 mg/kg) exerted antidepressant properties in FST as well as increased locomotor activity in the open field test. Chronic administration of EMD 386088 (2.5 mg/kg) significantly improved the learning deficit in OB rats without affecting performance in Sham-operated (SH) animals in the passive avoidance test, and reduced OB-related rats' locomotor hyperactivity, but did not change the number of rearing + peeping episodes. The obtained findings suggest that EMD 386088 produces antidepressant-like activity after systemic acute and chronic 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, Cracow, Poland, m.jastrzebska-wiesek@uj.edu.pl.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Jastrzębska-Więsek
authors.forename: Agata
authors.initials: A
authors.lastname: Siwek
authors.forename: Anna
authors.initials: A
authors.lastname: Partyka
authors.forename: Bernadeta
authors.initials: B
authors.lastname: Szewczyk
authors.forename: Magdalena
authors.initials: M
authors.lastname: Sowa-Kućma
authors.forename: Anna
authors.initials: A
authors.lastname: Wasik
authors.forename: Marcin
authors.initials: M
authors.lastname: Kołaczkowski
authors.forename: Anna
authors.initials: A
authors.lastname: Wesołowska
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D009043:Motor Activity / Q000187:drug effects; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D013550:Swimming
chemical_list: C534240:5-chloro-2-methyl-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole; D000928:Antidepressive Agents; D007211:Indoles; D011725:Pyridines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C097216:serotonin 6 receptor