title: The 5-HT6 receptor agonist EMD 386088 produces antidepressant and anxiolytic effects in rats after intrahippocampal administration.
abstract: BACKGROUND
  Preclinical data suggest a possible role for 5-HT6 receptors in depression and anxiety. However, the results of pharmacological studies are equivocal since both blockade and stimulation of 5-HT6 receptors may evoke antidepressant- and anxiolytic-like effects.
  
  
  OBJECTIVE
  In the present study, the effects of the 5-HT6 receptor agonist EMD 386088, administered intrahippocampally (i.hp.) to rats, were assessed in behavioral tests commonly used for evaluating antidepressant- and anxiolytic-like activities.
  
  
  RESULTS
  EMD 386088 (10 and 20 μg, i.hp.) exerted a significant antidepressant-like effect as revealed by decreased duration of rats' immobility in the forced swim test. This effect was blocked by systemic administration of the selective 5-HT6 receptor antagonist SB-399885. Additionally, the anxiolytic-like activity was demonstrated in the Vogel conflict and elevated plus maze tests, as EMD 386088 reduced the number of punished responding (5-20 μg, i.hp.) and increased the percentage of open arm entries (10 and 20 μg, i.hp.). The tested 5-HT6 agonist (5-20 μg, i.hp.) affected neither distance traveled in the open field test nor motor coordination assessed in the rotarod test.
  
  
  CONCLUSIONS
  The results of the present study demonstrate that the 5-HT6 agonist produces antidepressant- and anxiolytic-like effects and that the hippocampus could be one of the brain regions involved in this action.
authors.affiliation: Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Krakow, Poland. nikifor@if-pan.krakow.pl
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Nikiforuk
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kos
authors.forename: Anna
authors.initials: A
authors.lastname: Wesołowska
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013550:Swimming
chemical_list: C534240:5-chloro-2-methyl-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole; D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D007211:Indoles; D011725:Pyridines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C097216:serotonin 6 receptor