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J Toxicol Sci. 1992 May;17(2):81-90.

Behavioral evaluation of psycho-pharmacological and psychotoxic actions of methylxanthines by ambulatory activity and discrete avoidance in mice.

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Division for Behavior Analysis, Gunma University School of Medicine, Maebashi, Japan.


The behavioral effects of methylxanthines, caffeine, theophylline and theobromine, were compared by means of ambulatory activity and discrete lever-press avoidance response in mice. The single oral administration of 10-100 mg/kg of caffeine, 30-300 mg/kg of theophylline, and 10 mg/kg of theobromine significantly increased the mouse's ambulatory activity. However, 1000 mg/kg of theobromine decreased the activity. The ambulation-increasing effect of methamphetamine (2 mg/kg s.c.) was enhanced by coadministration with caffeine (3-100 mg/kg), theophylline (10-300 mg/kg), and theobromine (10-100 mg/kg). On the other hand, comparatively higher doses of caffeine (up to 30 mg/kg) slightly but significantly decreased the avoidance rate without eliciting any significant change in the response rate. Theobromine significantly decreased the response rate at higher than 300 mg/kg, and the avoidance rate at higher than 100 mg/kg. Furthermore, 1000 mg/kg of theobromine was much toxic for mice, i.e., half mice died within a few hr after the end of the 1-hr avoidance session. Theophylline did not produce any significant change in the avoidance response at the dose range of 3-300 mg/kg. These results may indicate the relative order of the centrally stimulant and/or behavioral toxic actions of methylxanthines in human.

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