Related Experiment Videos
Sensitivity of inbred mice to methylxanthines is not determined by plasma xanthine concentration
Abstract:
Male CBA/J and SWR/J mice were tested with doses of caffeine, theophylline and 8-p-sulfophenyltheophylline (xanthine). Caffeine produced dose-related decreases in locomotor activity and colonic temperatures in SWR/J mice. However, caffeine produced increases in locomotor activity and failed to lower the body temperature of CBA/J mice. Theophylline produced a decrease in body temperature of SWR/J mice. Comparison of brain caffeine levels demonstrated no difference in brain pharmacokinetics. The peripherally active xanthine failed to alter body temperature at the same molar dose as that of theophylline. These data clearly demonstrate that genetic differences in the effects of methylxanthine are due to inherent differences in the central nervous system sensitivity of the two strains. The data further indicate that while differences in xanthine metabolism may occur in inbred mice, these differences are not a major factor in the acute, peak plasma level, effects of xanthines.
Insights
Genetic differences in mouse strains cause varied responses to methylxanthines like caffeine. Central nervous system sensitivity, not metabolism, explains these distinct effects on activity and body temperature.
Area of Science:
- Pharmacology
- Neuroscience
- Genetics
Background:
- Methylxanthines, including caffeine and theophylline, are widely consumed stimulants.
- Individual responses to methylxanthines can vary significantly.
- Genetic factors are suspected to influence these variations.
Purpose of the Study:
- To investigate the impact of genetic background on the central and peripheral effects of methylxanthines.
- To determine whether differences in central nervous system sensitivity or metabolism underlie strain-specific responses.
Main Methods:
- CBA/J and SWR/J mice were administered caffeine, theophylline, and 8-p-sulfophenyltheophylline.
- Locomotor activity, colonic temperature, and brain caffeine levels were measured.
- Pharmacokinetic comparisons were made between strains.
Main Results:
- Caffeine decreased activity and temperature in SWR/J mice but increased activity in CBA/J mice.
- Theophylline reduced body temperature in SWR/J mice.
- No significant differences in brain caffeine pharmacokinetics were observed between strains.
- A peripherally acting xanthine did not affect body temperature, suggesting central mechanisms.
Conclusions:
- Genetic variations in central nervous system sensitivity to methylxanthines are the primary driver of differential effects between mouse strains.
- Differences in methylxanthine metabolism are not a major factor in acute, peak plasma level effects.