Anxiolytic and antidepressant-like activities of the novel and potent non-imidazole histamine H3 receptor antagonist ST-1283

Amine Bahi, Johannes Stephan Schwed, Miriam Walter, Holger Stark, Bassem Sadek

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)

Abstract

Previous studies have suggested a potential link between histamine H3 receptors (H3R) signaling and anxiolytic-like and antidepressant-like effects. The aim of this study was to investigate the acute effects of ST-1283, a novel H3R antagonist, on anxiety-related and depression-related behaviors in comparison with those of diazepam and fluoxetine. The effects of ST-1283 were evaluated using the elevated plus maze test, open field test, marbles burying test, tail suspension test, novelty suppressed feeding test, and forced swim test in male C57BL/6 mice. The results showed that, like diazepam, ST-1283 (7.5 mg/kg) significantly modified all the parameters observed in the elevated plus maze test. In addition, ST-1283 significantly increased the amount of time spent in the center of the arena without altering general motor activity in the open field test. In the same vein, ST-1283 reduced the number of buried marbles as well as time spent digging in the marbles burying test. The tail suspension test and forced swim test showed that ST-1283 was able to reduce immobility time, like the recognized antidepressant drug fluoxetine. In the novelty suppressed feeding test, treatment with ST-1283 decreased latency to feed with no effect on food intake in the home cage. Importantly, pretreatment with the H3R agonist R-α-methylhistamine abrogated the anxiolytic and antidepressant effects of ST-1283. Taken together, the present series of studies demonstrates the novel effects of this newly synthesized H3R antagonist in a number of preclinical models of psychiatric disorders and highlights the histaminergic system as a potential therapeutic target for the treatment of anxiety-related and depression-related disorders.

Original languageEnglish
Pages (from-to)627-637
Number of pages11
JournalDrug Design, Development and Therapy
Volume8
DOIs
Publication statusPublished - May 28 2014

Keywords

  • Anxiety
  • Depression
  • Histamine
  • R-α-methylhistamine
  • ST-1283

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery

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