Abstract
Caffeine is a common psychoactive constituent of coffee, carbonated beverages, and over-the-counter medications. This study examined the effects of chronic caffeine exposure on the behavioral response to acute administrations of psychostimulant drugs on ambulatory activity and on the pharmacological characteristics of nicotine discrimination in rats. Rats were maintained continuously on caffeine added to the drinking water at a concentration of 0.25 or 1.0 mg/ml that resulted in plasma caffeine concentrations ranging from 0.37 to 5.95 μg/ml. Rats maintained on tap water served as control groups. Exposure to the lower caffeine concentration (0.25 mg/ml) potentiated stimulatory effects of nicotine, amphetamine, and cocaine on ambulatory activity and failed to produce tolerance to the acute stimulatory effects of caffeine. In contrast, exposure to the higher caffeine concentration (1.0 mg/ml) did not alter the effects of the psychomotor stimulants on ambulatory behaviors but resulted in the development of complete, insurmountable tolerance to the acute stimulatory effects of caffeine. In the nicotine discrimination paradigm (0.4 mg/kg, training dose, a fixed-ratio 10 schedule of food delivery in a two-lever choice paradigm), rats exposed to the lower, but not to the higher, caffeine concentration acquired the nicotine discrimination significantly faster and were more sensitive to the effects of amphetamine and cocaine in substitution tests than water-drinking rats. Caffeine exposure did not change pharmacokinetic properties of nicotine (i.e., plasma levels, metabolism). In summary, exposure to two different caffeine solutions within a range of plasma levels observed in humans resulted in quantitatively distinct changes in psychostimulant-induced nonoperant and operant measures of behavior. These results suggest that dietary consumption of moderate doses of caffeine may be associated with enhanced reactions to some psychostimulants.
Footnotes
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Send reprint requests to: Maciej Gasior, M.D., Ph.D., Behavioral Pharmacology Program, Department of Psychiatry, Alcohol and Drug Abuse Research Center, McLean Hospital, Harvard Medical School, 115 Mill St., Belmont, MA 02178-9106. E-mail:mgasior{at}mclean.harvard.edu
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↵1 Visiting Fellow in the National Institutes of Health granted from the Fogarty International Center, Bethesda, MD. Permanent affiliation: Department of Pharmacology, Medical University School, Lublin, Poland. Current address: Department of Psychiatry, Behavioral Pharmacology Program, McLean Hospital, Harvard Medical School, Belmont MA.
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↵2 Visiting Fellow in the National Institutes of Health granted from the Fogarty International Center, Bethesda, MD. Permanent affiliation: Department of Internal Medicine, Medical University School, Lublin, Poland.
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↵3 Summer research fellow supported by a National Institutes of Health Intramural Research Training Award. Current affiliation: Virginia Polytechnic Institute and State University, Blacksburg, VA.
- Abbreviations:
- CAFF
- caffeine
- FR
- fixed-ratio
- Received April 4, 2000.
- Accepted August 24, 2000.
- U.S. Government
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