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Intracerebral infusion of 3 H‐dopamine and 3 H‐mannitol in the striatum of halothane‐anaesthetized male rats.A dual‐probe microdialysis study of long‐distance diffusion
Author(s) -
Höistad M.,
Kehr J.,
Andbjer B.,
Jansson A.,
Fuxe K.
Publication year - 2000
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2000.00141.x
Subject(s) - microdialysis , mannitol , chemistry , dopamine , halothane , tritiated water , in vivo , striatum , extracellular fluid , extracellular , chromatography , endocrinology , biochemistry , tritium , medicine , biology , physics , microbiology and biotechnology , organic chemistry , nuclear physics
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 n m 3 H‐DA) or mannitol (1.5 μ m 3 H‐mannitol) was infused continuously for 5 h, while samples were collected from the other probe. Samples (10 μl) were counted by liquid scintillation. For the DA‐infused rats, another 10 μL 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 β‐decay. The total transfer of 3 H‐labelled compounds described the overall effect of cellular uptake, metabolism and clearance into the microcirculation, and was compared with that of an extracellular marker, 3 H‐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 3 H‐mannitol were lower than those following the 3 H‐dopamine infusion in both control or 6‐OHDA‐lesioned rats. However, it was not possible to detect any unmetabolized 3 H‐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.