Intracerebral infusion of H-dopamine and H-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 3H-DA) or mannitol (1.5 microM 3H-mannitol) was infused continuously for 5 h, while samples were collected from the other probe. Samples (10 microl) were counted by liquid scintillation. For the DA-infused rats, another 10 microL 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 3H-labelled compounds described the overall effect of cellular uptake, metabolism and clearance into the microcirculation, and was compared with that of an extracellular marker, 3H-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, t50%, was in all cases lower in 6-OHDA-treated rats compared with control. In addition, the t50% values of 3H-mannitol were lower than those following the 3H-dopamine infusion in both control or 6-OHDA-lesioned rats. However, it was not possible to detect any unmetabolized 3H-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.
Höistad
M
M
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. Malin.Hoistad@neuro.ki.se
Kehr
J
J
Andbjer
B
B
Jansson
A
A
Fuxe
K
K
D018685:Anesthetics, Inhalation; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D003714:Denervation; D004058:Diffusion; D004234:Diuretics, Osmotic / Q000493:pharmacokinetics*; D004298:Dopamine / Q000493:pharmacokinetics*; D005110:Extracellular Space / Q000378:metabolism; D006221:Halothane; D008297:Male; D008353:Mannitol / Q000493:pharmacokinetics*; D017551:Microdialysis; D016627:Oxidopamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013565:Sympatholytics; D014316:Tritium
D018685:Anesthetics, Inhalation; D004234:Diuretics, Osmotic; D013565:Sympatholytics; D014316:Tritium; D008353:Mannitol; D016627:Oxidopamine; D006221:Halothane; D004298:Dopamine