Role of the serotonergic system in reduced pulmonary function after exposure to methamphetamine

Sandra M. Wells, Mary C. Buford, Virginia M. Porter, Heather L. Brunell, Melisa Bunderson-Schelvan, Andrew B. Nevin, Fernando Cardozo-Pelaez, Andrij Holian

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Although use of methamphetamine (MA) by smoking is the fastest growing method of administration, very limited data are available describing the effects of smoked MA. Using a murine inhalation exposure system, we explored the pulmonary effects of low-dose acute inhalation exposure to MA vapor (smoke). Inhalation of MA vapor resulted in transiently reduced pulmonary function, as measured by transpulmonary resistance, dynamic compliance, and whole-body plethysmography compared with unexposed control animals. These changes were associated with an approximately 34% reduction in serotonin (5-hydroxytryptamine [5-HT]) metabolism/inactivation to 5-hydroxyindolacetic acid, and a nearly 40% reduction in monoamine oxidase (MAO)-A activity in the lung. Pretreatment of mice with a selective 5-HT reuptake inhibitor completely ablated the MA-induced changes in pulmonary function, confirming a key role for the 5-HT transporter (serotonin transporter [SERT]) and the serotonergic system in this effect. Immunofluorescent staining of mouse lung tissue confirmed high expression of SERT in airway epithelial cells. Using mouse airway epithelial cell line, LA-4, and purified human MAO-A, it was demonstrated that MA impedes 5-HT metabolism through direct inhibition of MAO-A activity in vitro. Together, these data demonstrate that low-dose exposure to MA results in reduced pulmonary function mediated via SERT and subsequent perturbation of 5-HT metabolism in the lung. This supports a role for the serotonergic system in MA-mediated pulmonary effects.

Original languageEnglish (US)
Pages (from-to)537-544
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume42
Issue number5
DOIs
StatePublished - May 1 2010
Externally publishedYes

Keywords

  • Lung
  • Monoamine oxidase A
  • Selective serotonin reuptake inhibitor
  • Serotonin transporter

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