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Antidepressant-like effects of serotonin type-3 antagonist, ondansetron: an investigation in behaviour-based rodent

Rajkumar Ramamoorthy1, Mahesh Radhakrishnan, Minasri Borah

  • 1Pharmacy Group, Birla Institute of Technology & Science, Faculty Division - III, Pilani, Rajasthan, India. rajkumarrna@yahoo.com

Behavioural Pharmacology
|January 16, 2008
PubMed

Insights

Ondansetron (OND), a 5-HT3 receptor antagonist, demonstrates antidepressant-like effects in behavioral tests. Chronic OND enhances other antidepressants and modulates anxiety-related behaviors, suggesting therapeutic potential.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Behavioral Science

Background:

  • Ondansetron (OND) is a 5-HT3 receptor antagonist primarily used for chemotherapy-induced nausea and emesis.
  • The role of 5-HT3 receptors in mood regulation and potential antidepressant effects of OND is not fully understood.

Purpose of the Study:

  • To investigate the antidepressant potential of ondansetron (OND) using established behavioral models in rodents.
  • To explore the interaction of OND with other antidepressant medications and its effects on anxiety-related behaviors.

Main Methods:

  • Acute and chronic treatments of OND were administered to mice and rats.
  • Behavioral assays included spontaneous locomotor activity, forced swim test, tail suspension test, open field test, and elevated plus maze.
  • Drug interaction studies were performed with fluoxetine, venlafaxine, desipramine, 8-hydroxy-2-(di-n-propylamino) tetralin, and paroxetine.

Main Results:

  • OND exhibited a biphasic, dose-dependent antidepressant-like effect, peaking at 0.1 microg/kg in forced swim and tail suspension tests.
  • Chronic OND pretreatment potentiated the antidepressant effects of fluoxetine and venlafaxine.
  • OND administration reversed hyperactivity and reduced anxiety-like behaviors in bulbectomized rats.

Conclusions:

  • Ondansetron displays antidepressant-like properties, potentially mediated via postsynaptic 5-HT3 receptors.
  • OND may enhance the efficacy of certain existing antidepressant drugs.
  • The findings suggest OND as a potential therapeutic agent for depression and anxiety disorders.

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