A method to evaluate the diffusion rate of drugs from a microdialysis probe through brain tissue

For interpretation of microdialysis experiments in which compounds are applied retrodialysis, it is important to have information about the migration rate of the infused compounds. Here we describe a dual-probe microdialysis method that can be used to evaluate the penetration rate of the infused drug. The basic idea is that not the drug itself is assayed, but that its pharmacological effect is recorded by a second probe positioned at a fixed distance (1 mm) of the infusion probe. Using this approach several compounds, each known to induce specific changes in the extracellular levels of dopamine, were infused into the striatum of the rat. The results indicate that the penetration rate of the pharmacological effect of infused compounds differed widely. No effects were seen at the second probe when high potassium chloride was infused. Apparently dopamine was not able to migrate into brain tissue over a distance of 1 mm. Low penetration rates were observed for the dopamine antagonist sulpiride, the dopamine agonist LY17155, and for amphetamine and nomifensine. A very high penetration rate was observed in case of tetrodotoxin. The fast effects of TTX could also be explained by remote inhibition of neurons passing along the infusion probe. The present study showed that most of the compounds have rather slow infusion rates, indicating that relatively high infusion concentrations are needed (1-10 mM) to reach substantial brain concentrations at a distance of 1 mm from the infusion probe.