Two simultaneously working storage pools of dopamine in mouse caudate and nucleus accumbens.

1. The dynamics of the decline of evoked dopamine overflow after repeated electrical stimulation (2 or 4 s train duration, 50 Hz) of the median forebrain bundle were investigated by means of in vivo voltammetry in mouse caudate and nucleus accumbens. An unexpected effect-slowing of the rate of dopamine decline after repeated stimulation at short (10 s or less) between-stimulation intervals, and an increase in the absolute amount of dopamine released at the beginning of the repeated stimulation-was found. 2. After the evoked dopamine overflow had been reduced by alpha-methyl-p-tyrosine (AMPT), repeated stimulation at intervals of 5 s increased dopamine release to each subsequent stimulation applied. 3. It is proposed that there are two compartments involved in dopamine storage. Both contribute to the release of dopamine, however, they may be separated artificially by either applying stimulation at short intervals or by depletion of intracellular dopamine. 4. The first releasable pool (newly synthesized, AMPT-sensitive) provides dopamine for the release after a single stimulation or repeated stimulation, being independent of whether the first stimulation is succeeded quickly by a second. It is also independent of between-stimulation interval. 5. The second pool (AMPT-insensitive storage pool) is progressively activated after repeated stimulation. The duration of the between-stimulation intervals is the crucial factor for the activation of this pool.