Antidepressant-like effect of a novel 5-HT3 receptor antagonist N-(benzo[d] thiazol-2-yl)-3-ethoxyquinoxalin-2-carboxamide 6k using rodents behavioral battery tests

Yeshwant Kurhe, Radhakrishnan Mahesh, Thangaraj Devadoss, Deepali Gupta

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Objective: To investigate the antidepressant-like effect of N-(benzo[d] thiazol-2-yl)-3-ethoxyquinoxalin-2-carboxamide 6k, a 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist using rodents behavioral battery tests. Materials and Methods: 6k screening was performed with behavioral assays for depression-like forced swim test (FST) at several single doses (0.25-4 mg/kg, intraperitoneal injection (i.p.)) to test the potency of 6k, in which 2 and 4 mg/kg doses were found to be most effective and hence, in further behavioral assays including mechanistic model like 5-hydroxytryptophan (5-HTP)-induced head twitches was performed in mice at acute doses of 6k (2 and 4 mg/kg, i.p.). Furthermore, olfactory bulbectomy (OBX), a surgical model-induced behavioral alterations was performed in rats, and the effect of 6k administered orally (2 and 4 mg/kg, p.o.) after subchronic treatment for 14 days starting from day 15 of postsurgery was examined by percent sucrose preference test and modified open field test (OFT). Results: 6k (1, 2, and 4 mg/kg, i.p.) reduced the immobility time and increased the swimming behavior in FST without affecting the baseline locomotor score showing antidepressant-like effect. 5-HTP-induced head twitch response was potentiated by 6k (2 and 4 mg/kg, i.p.), which indicated rise in the serotonergic neurotransmission in the brain. 6k (2 and 4 mg/kg, p.o.) showed anti-anhedonia effect by increasing the sucrose consumption and reversed the behavioral alterations when exposed to modified open field in OBX rats after subchronic treatment for 14 days, thus exhibiting antidepressant-like effect. Conclusion: 6k attenuated the behavioral derangement in rodents-based behavioral battery tests for depression, indicating antidepressant-like potential.

Original languageEnglish (US)
Pages (from-to)197-202
Number of pages6
JournalJournal of Pharmacology and Pharmacotherapeutics
Volume5
Issue number3
DOIs
StatePublished - 2014
Externally publishedYes

Keywords

  • N-(benzo[d] thiazol-2-yl)-3-ethoxyquinoxalin-2-carboxamide 6k
  • depression
  • forced swim test
  • head twitches
  • sucrose preference

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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