Dose dependency and reversibility of serotonin-induced valvular heart disease in rats

Cardiovasc Toxicol. 2009 Sep;9(3):134-41. doi: 10.1007/s12012-009-9046-2. Epub 2009 Jul 16.


Serotonergic drugs may lead to valvular heart disease in humans and more recently also in rats. Although clinical data suggest that dose dependency and reversibility after drug cessation might occur, proof of this is lacking. For that purpose, a total of 106 rats were prospectively enrolled: 22 control animals and 7 groups of 12 rats that received daily subcutaneous serotonin injections (5, 10, 20, 30, 40, 50 and 60 mg/kg respectively) for 12 weeks. At 12 weeks, half of the animals of each group were killed for histological analysis, whereas the remaining rats were further followed (without serotonin injections) for an additional 8 weeks. After 12 weeks of serotonin treatment, aortic and mitral regurgitation (AR, MR) were more frequently observed in the high dose groups (>30 mg/kg) compared to controls. Moreover, aortic and mitral valves were also thicker in the high dose groups compared to controls. After 8 weeks free of serotonin injections, AR and MR were no longer significantly higher than controls. Moreover, aortic and mitral valve thickness had normalized, returning to control levels. In conclusion, this study provides evidence for a dose-dependent valvular toxicity of serotonergic drugs, which appears to be reversible after drug withdrawal.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aortic Valve / drug effects
  • Aortic Valve / pathology
  • Disease Models, Animal*
  • Dose-Response Relationship, Drug
  • Heart Valve Diseases / chemically induced*
  • Heart Valve Diseases / pathology*
  • Male
  • Mitral Valve / drug effects
  • Mitral Valve / pathology
  • Prospective Studies
  • Rats
  • Rats, Wistar
  • Remission, Spontaneous
  • Serotonin / administration & dosage*
  • Serotonin / toxicity*
  • Time Factors


  • Serotonin