Further studies on the behavioural and biochemical interaction between caffeine and L-DOPA.

Abstract

Mice, pretreated with the inhibitor of peripheral DOPA decarboxylase MK 486, were given caffeine, 25 mg/kg, or L-DOPA, 125 mg/kg, or both. The locomotor activity of the animals recorded for 2 h, doubled after caffeine whereas the effect of L-DOPA varied from depression to a slight hyperactivity. In combination the two drugs produced a tenfold increase in locomotor activity. The accumulation of dopamine in the brain, and the levels of DOPA in both brain and plasma following administration of L-DOPA, all increased when caffeine was given beforehand. However, caffeine did not modify the effects of L-DOPA on brain noradrenaline, 3-methoxytyrosine, 5-hydroxytryptamine, and 5-hydroxyindolacetic acid significantly. In some experiments3H-tyrosine was given before MK 486, caffeine and/or L-DOPA in order to label the central catecholamine stores. The disappearance of brain3H-NA and3H-DA following L-DOPA was not significantly changed by caffeine. From these and earlier data it is suggested that part of the potentiating effect of caffeine on the L-DOPA induced motility is due to the increased cerebral level of dopamine and part to a catecholamine-receptor sensitizing effect of caffeine.