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

Neuropharmacology. 2014 Oct:85:253-62. doi: 10.1016/j.neuropharm.2014.05.036. Epub 2014 Jun 4.

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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Anxiety / drug therapy*
  • Anxiety / physiopathology
  • Conflict, Psychological
  • Dose-Response Relationship, Drug
  • Drinking Behavior / drug effects
  • Drinking Behavior / physiology
  • Exploratory Behavior / drug effects
  • Exploratory Behavior / physiology
  • Guinea Pigs
  • Indoles / pharmacology*
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Neuropsychological Tests
  • Pain Threshold / drug effects
  • Pain Threshold / physiology
  • Pyridines / pharmacology*
  • Random Allocation
  • Rats, Wistar
  • Receptors, GABA-A / metabolism
  • Receptors, Serotonin / metabolism
  • Receptors, Serotonin, 5-HT3 / metabolism
  • Serotonin Receptor Agonists / pharmacology*

Substances

  • 5-chloro-2-methyl-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole
  • Anti-Anxiety Agents
  • Indoles
  • Pyridines
  • Receptors, GABA-A
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT3
  • Serotonin Receptor Agonists
  • serotonin 6 receptor