Serotonin involvement in Rhodiola rosea attenuation of nicotine withdrawal signs in rats

Phytomedicine. 2012 Sep 15;19(12):1117-24. doi: 10.1016/j.phymed.2012.07.001. Epub 2012 Aug 24.


Rhodiola rosea has been used for centuries in the traditional medicine to stimulate nervous system, to enhance physical and mental performance and to treat fatigue. It is known that administration of Rhodiola rosea extract elicits antidepressant activity, but the mechanism of action still remains unclear. Evidence from animal models and human studies show that nicotine reduces symptoms of depression and that nicotine cessation induces depressive-like symptoms. We investigated the effects of Rhodiola rosea on nicotine withdrawal signs. Nicotine dependence was induced by subcutaneous nicotine injection (2 mg/kg, four times daily) for 14 days. Another group of animals treated with nicotine (for 14 days) and successively with Rhodiola rosea extract was co-administered with selective 5-HT receptorial antagonist WAY 100635 (1 mg/kg). After nicotine withdrawal animals were evaluated for behavioural parameters (locomotor activity, abstinence signs, marble burying test), diencephalic serotonin metabolism and serotonin receptor-1A expression. Results show a significant increase of 5-HT content in N treated with R. rosea, with a significant increase of serotonin receptor 1A, suggesting an involvement of serotonin in beneficial effects of R. rosea on suffering produced by nicotine withdrawal.

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Behavior, Animal / drug effects
  • Brain / drug effects
  • Brain / metabolism
  • Depression / drug therapy*
  • Male
  • Nicotine / administration & dosage*
  • Phytotherapy*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Rhodiola*
  • Serotonin / metabolism*
  • Substance Withdrawal Syndrome / drug therapy*
  • Substance Withdrawal Syndrome / metabolism
  • Tobacco Use Disorder / drug therapy
  • Tobacco Use Disorder / metabolism


  • Antidepressive Agents
  • Plant Extracts
  • Receptor, Serotonin, 5-HT1A
  • Serotonin
  • Nicotine