4-phenylselenyl-7-chloroquinoline, a novel multitarget compound with anxiolytic activity: Contribution of the glutamatergic system

J Psychiatr Res. 2017 Jan:84:191-199. doi: 10.1016/j.jpsychires.2016.10.007. Epub 2016 Oct 11.

Abstract

A growing body of evidence demonstrates that quinoline compounds have attracted much attention in the field of drug development. Accordingly, 4-phenylselenyl-7-chloroquinoline (4-PSQ) is a new quinoline derivative containing selenium, which showed a potential antioxidant, antinociceptive and anti-inflammatory effect. The present study was undertaken to evaluate the anxiolytic-like properties of 4-PSQ. Mice were orally pretreated with 4-PSQ (5-50 mg/kg) or vehicle, 30 min prior to the elevated plus-maze (EPM), light-dark (LDT) or open field (OFT) tests. A time-response curve was carried out by administration of 4-PSQ (50 mg/kg) at different times before the EPM test. The involvement of glutamate uptake/release and Na+, K+-ATPase activity in the anxiolytic-like effect was investigated in cerebral cortices. In addition, the effectiveness of acute treatment with 4-PSQ was evaluated in a model of kainate (KA)-induced anxiety-related behavior. Finally, acute toxicity of this compound was investigated. 4-PSQ produced an anxiolytic-like action, both in EPM and LDT. In OFT, 4-PSQ did not affect locomotor and exploratory activities. 4-PSQ anxiolytic-like effect started at 0.5 h and remained significant up to 72 h after administration. Treatment with 4-PSQ reduced [3H] glutamate uptake, but the [3H] glutamate release and Na+, K+-ATPase activity were not altered. KA-induced anxiety-related behavior was protected by 4-PSQ pretreatment. Additionally, 4-PSQ exposure did not alter urea levels, aspartate (AST) and alanine aminotrasferase (ALT) activities in plasma. Parameters of oxidative stress in brain and liver of mice were not modified by 4-PSQ. Taken together these data demonstrated that the anxiolytic-like effect caused by 4-PSQ seems to be mediated by involvement of the glutamatergic system.

Keywords: Anxiety; Glutamate; Kainate; Mice; Quinoline; Selenium.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Anxiety Agents / chemistry
  • Anti-Anxiety Agents / pharmacology*
  • Anti-Anxiety Agents / toxicity
  • Anxiety / drug therapy*
  • Anxiety / metabolism
  • Brain / drug effects
  • Brain / metabolism
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Excitatory Amino Acid Agents / chemistry
  • Excitatory Amino Acid Agents / pharmacology*
  • Excitatory Amino Acid Agents / toxicity
  • Exploratory Behavior / drug effects
  • Exploratory Behavior / physiology
  • Glutamic Acid / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice
  • Molecular Structure
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Organoselenium Compounds / chemistry
  • Organoselenium Compounds / pharmacology*
  • Organoselenium Compounds / toxicity
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Psychological Tests
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Quinolines / toxicity
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Time Factors
  • Tritium

Substances

  • 4-phenylselenyl-7-chloroquinoline
  • Anti-Anxiety Agents
  • Excitatory Amino Acid Agents
  • Organoselenium Compounds
  • Quinolines
  • Tritium
  • Glutamic Acid
  • Sodium-Potassium-Exchanging ATPase