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      Tolerance to caffeine-induced stimulation of locomotor activity in rats.

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      The Journal of pharmacology and experimental therapeutics

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          Abstract

          The objective of this study was to quantify the rate and extent of tolerance development and loss of tolerance to caffeine-induced stimulation of locomotor activity in rats as a function of average daily caffeine dosage. Adult male rats were maintained chronically on 0.25, 0.5 or 1.0 mg/ml of caffeine in their drinking water by the method of scheduled access. These concentrations of caffeine yielded average daily doses of 19, 36 and 67 mg/kg, respectively. A control group received scheduled access to drug-free drinking water. A dose of 30 mg/kg of caffeine was administered by gavage periodically to all rats before, after the start of and following withdrawal from chronic caffeine treatment. Locomotor activity was measured either for 3 hr immediately after caffeine administration or for 30 min beginning 35 min after caffeine administration. In addition, dose-effect relationships for caffeine (5.6-175 mg/kg) were determined 3 to 5 weeks after the start of chronic drug treatment and were redetermined 2 to 4 weeks after withdrawal. Complete and reversible tolerance developed in the groups receiving the two higher daily doses of caffeine; nearly complete tolerance developed in the group receiving the lowest dose. Dose-effect curves were shifted downward and tolerance was not surmountable by increasing the dose of caffeine. Significant tolerance developed within 1 to 3 days of the start of chronic caffeine exposure and was lost within 3 to 4 days after the cessation of drug treatment. These results are reminiscent of a classical tachyphylaxis.

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          Author and article information

          Journal
          J. Pharmacol. Exp. Ther.
          The Journal of pharmacology and experimental therapeutics
          0022-3565
          0022-3565
          Aug 1986
          : 238
          : 2
          Article
          3735131
          9e3bb362-91a0-44e5-8b12-d469532b93aa
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