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Inherent differences in sensitivity to methylxanthines among inbred mice
Abstract:
The behavioral effects of caffeine, theophylline, paraxanthine, and theobromine on locomotor activity were analyzed in four strains of inbred mice that were previously shown to differ in their acute toxic responses to caffeine administered at high dosages. Dose response curves for the effects of caffeine, theophylline, paraxanthine and theobromine on locomotor activity were established in CBA/J, C57BL/6J, DBA/2J and SWR/J strains of inbred mice. Paraxanthine was the maximally effective methylxanthine in the CBA/J, DBA/2J and SWR/J strains, while in the C57BL/6J strain, caffeine was the maximally effective methylxanthine. Theophylline failed to stimulate locomotor activity in the C57BL/6J strain and theobromine failed to stimulate activity in all of the strains tested. Decreases in locomotor activity were seen at the 100 mg/kg dose of caffeine in the C57BL/6J mice and at the 100 mg/kg dose of theophylline in the C57BL/6J, DBA/2J and SWR/J strains. Theobromine produced decreases in locomotor activity in the C57BL/6J, DBA/2J and SWR/J strains of mice. In contrast to the other methylxanthines, paraxanthine failed to decrease activity across the range of doses tested (1.0-150 mg/kg). These data suggest that the methylxanthines have genetically specified multiple modes of action upon locomotor activity and that the use of genetically distinct strains of mice may have important value in the neurochemical and pharmacological dissection of methylxanthine-induced behavioral effects.
Insights
Caffeine and related compounds affect mouse activity differently across genetic strains. Paraxanthine and caffeine were most effective at increasing activity, while theobromine and theophylline showed varied effects.
Area of Science:
- Pharmacology
- Neuroscience
- Genetics
Background:
- Caffeine and its metabolites, methylxanthines, are widely consumed stimulants.
- Previous studies indicated genetic differences in mouse responses to caffeine toxicity.
Purpose of the Study:
- To investigate the behavioral effects of caffeine, theophylline, paraxanthine, and theobromine on locomotor activity in four distinct inbred mouse strains.
- To determine if genetic background influences the dose-response relationships of these methylxanthines.
Main Methods:
- Dose-response curves were established for four methylxanthines in CBA/J, C57BL/6J, DBA/2J, and SWR/J mice.
- Locomotor activity was measured to assess stimulant and depressant effects.
Main Results:
- Paraxanthine was the most effective stimulant in CBA/J, DBA/2J, and SWR/J mice; caffeine was most effective in C57BL/6J mice.
- Theophylline and theobromine showed limited or no stimulatory effects, and often decreased activity at higher doses across strains.
- Paraxanthine uniquely failed to decrease locomotor activity within the tested dose range.
Conclusions:
- Methylxanthines exhibit genetically determined, multiple modes of action on locomotor activity.
- Genetically distinct mouse strains are valuable tools for dissecting the neurochemical and pharmacological mechanisms underlying methylxanthine-induced behaviors.