Fluoxetine Attenuates Chronic Methamphetamine-Induced Pulmonary Arterial Remodelling: Possible Involvement of Serotonin Transporter and Serotonin 1B Receptor

Basic Clin Pharmacol Toxicol. 2013 Feb;112(2):77-82. doi: 10.1111/j.1742-7843.2012.00933.x.

Abstract

Epidemiological data have shown that methamphetamine (MA) abuse significantly increases the risk of developing pulmonary arterial hypertension (PAH). To investigate whether MA could induce PAH and its possible mechanism, rats were exposed daily to MA for 5 weeks in the absence or presence of fluoxetine. The results showed that the pulmonary arterial pressure was not significantly increased, but the pulmonary arterial remodelling was markedly developed in the MA exposure group. The protein expressions of the serotonin transporter (5-HTT) and 5-HT(1B) receptor were increased in the lungs and in the pulmonary arteries of MA-treated rats. Fluoxetine attenuated the pulmonary arterial remodelling and down-regulated the protein expression of 5-HTT and 5-HT(1B) receptor in pulmonary arteries of MA-treated rats. These findings suggest that fluoxetine has a novel potential suppressive effect on the chronic MA-induced pulmonary vascular remodelling and also suggest that 5-HTT and 5-HT(1B) receptor may be involved as part of its mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamine-Related Disorders / complications
  • Animals
  • Antidepressive Agents, Second-Generation / pharmacology
  • Down-Regulation / drug effects
  • Familial Primary Pulmonary Hypertension
  • Fluoxetine / pharmacology*
  • Hypertension, Pulmonary / etiology*
  • Hypertension, Pulmonary / pathology
  • Lung / drug effects
  • Lung / metabolism
  • Male
  • Methamphetamine / toxicity*
  • Pulmonary Artery / drug effects
  • Pulmonary Artery / metabolism
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT1B / genetics
  • Receptor, Serotonin, 5-HT1B / metabolism
  • Serotonin Plasma Membrane Transport Proteins / genetics
  • Serotonin Plasma Membrane Transport Proteins / metabolism*

Substances

  • Antidepressive Agents, Second-Generation
  • Receptor, Serotonin, 5-HT1B
  • Serotonin Plasma Membrane Transport Proteins
  • Fluoxetine
  • Methamphetamine