Intracerebral infusion of 3H-dopamine and 3H-mannitol in the striatum of halothane-anaesthetized male rats.: A dual-probe microdialysis study of long-distance diffusion

This report characterizes an in vivo intracerebral long-distance diffusion model using dual-probe microdialysis. Two probes 1 mm apart were implanted into the striatum of control and 6-hydroxydopamine (6-OHDA)-lesioned halothane-anaesthetized male rats. Either tritiated dopamine (500 nm H-3-DA) or mannitol (1.5 mu m H-3-mannitol) was infused continuously for 5 h, while samples were collected from the other probe. Samples (10 mu l) were counted by liquid scintillation. For the DA-infused rats, another 10 mu L was separated with high-pressure liquid chromatography (HPLC)-electrochemical detection into individual fractions containing 3,4-dihydroxy phenylacetic acid (DOPAC) and homovanillinic acid (HVA), and counted for beta-decay. The total transfer of H-3-labelled compounds described the overall effect of cellular uptake, metabolism and clearance into the microcirculation, and was compared with that of an extracellular marker, H-3-mannitol. The migration reached steady-state levels, generating an equilibrium between delivery and removal from the extracellular space. The half-time of the steady-state values, t(50%), was in all cases lower in 6-OHDA-treated rats compared with control. In addition, the t(50%) values of H-3-mannitol were lower than those following the H-3-dopamine infusion in both control or 6-OHDA-lesioned rats. However, it was not possible to detect any unmetabolized H-3-dopamine at the 1 mm distance. In conclusion, the dual-probe microdialysis approach proved to be a valid method to study in vivo diffusion and migration in the brain, and the intracerebral spread of compounds highly depends on the nature of the compound infused.