Effects of caffeine on monoaminergic systems in mouse brain.

Effects of caffeine on monoamine systems in the mouse brain were studied in three lines of experiments. First, concentrations of 10(-7) M to 10(-2) M of caffeine were tested for their potency in inhibiting the carriers involved in the neuronal uptake of dopamine, norepinephrine, and serotonin. The IC50 of caffeine in inhibiting the first two carriers was approximately 10(-2) M, and that in inhibiting the serotonin was 2 x 10(-3) M. Second, concentrations of 10(-5) M to 10(-3) M of caffeine were tested for their potency in affecting the in vitro KC1-induced release of [3H]dopamine from dopamine terminals in the striatum and from norepinephrine terminals in the hypothalamus, and the release of [3H]serotonin from serotonin terminals in the striatum. Little or no effect was observed. Third, caffeine was administered for 3 weeks to mice via their drinking water at 73, 123, and 162 mg/kg per day. No changes were found in their D2-dopaminergic, 5-HT2-serotonergic, or alpha 1-adrenergic receptors in the striatum or cerebral cortex as compared with animals on normal drinking water. All these neurochemical results are consonant with the interpretation of behavioral studies suggesting that caffeine is an only mildly stimulatory drug that should not be grouped with other psycho-stimulant drugs such as amphetamine and cocaine that do affect monoamine systems in the brain.