Mouse strain-specific acute respiratory effects of nicotine unrelated to nicotine metabolism

Abstract

Plethysmograph measurement of respiratory phenotypes provides a highly sensitive means to study nicotine response in experimental model animals. We measured average respiratory frequency, tidal volume, minute volume and inspiratory time in C3H/HeJ and C57BL/6J mice subcutaneously administered 0.35 and 0.70 mg/kg nicotine. Both mouse strains showed significantly altered respiratory and locomotion phenotypes relative to saline-injected controls when administered the higher dose, but only C57BL/6J responded to the lower nicotine dose. Respiratory and locomotion phenotypes rarely differed significantly by sex. To investigate whether the strain-specific differences in nicotine sensitivity were related to differences in clearance, we followed up by measuring nicotine clearance in C3H/HeJ and C57BL/6J mice (0.35 mg/kg subcutaneous) and found sex differences in both strains, but no difference between strains.

Keywords:

• Respiration
• ventilation
• nicotine
• mouse
• strain
• plethysmography

Acknowledgements

Thanks to Prof Evan Kharasch at Duke University for his guidance, comments on this article, and the use of his mass spectrometer. Thanks to Prof Qin Liu at Washington University in St Louis for assistance and the use of her plethysmograph.

Disclosure statement

No potential conflict of interest was reported by the author.

Additional information

Funding

This work was supported by the National Institute on Drug Abuse [grant K01 DA034035] and The Longer Life Foundation, a Reinsurance Group of America/Washington University Partnership.