Distribution of intracerebrally injected dopamine as studied by a punch-scintillation modeling technique

Three-dimensional distribution gradients of intracerebrally injected tritiated dopamine were calculated on the basis of concentrations in multiple punch-samples from sequential sections of Macaca fascicularis brain tissue. The monkey was pretreated systemically with a monoamine oxidase inhibitor to retard elimination. Gradients were best fit by cubic exponential equations relating concentration to distance from the center of the site. The concentration at the center, total amount of label, and total extent of the site injected just before perfusion were consistent with initial distribution in the extracellular space, if the volume fraction of the latter is estimated at 20%. The extent of distribution was distinctly greater in the mediolateral and dorsoventral dimensions than in the anteroposterior dimension. The total amount of label near the site decreased rapidly in the first few minutes after injection, then much more slowly, reaching about 30% of the injected amount after 2 h. Its distribution within the site changed steadily, the outer boundary gradually expanding and the peak at the center gradually decreasing. This pattern was consistent with an initial rapid dispersion by injection pressure and an initial loss of tritiated dopamine due to disruption of the blood-brain barrier at the center of the site, followed by a steady expansion of the site driven by diffusion and bulk flow.