Dose-dependent delivery of colchicine to the rat hippocampus by microdialysis

The time courses of the colchicine delivery and diffusion rate in the brain were studied by microdialysis in the rat. Microdialysis allowed the exposure of the brain tissue to colchicine to be regulated, unlike a bolus injection. Colchicine was infused directly into the dorsal hippocampus at 40 ng/m...

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Bibliographic Details
Published in:Neuroscience letters 1996-02, Vol.205 (1), p.9-12
Main Authors: Desrayaud, Sandrine, Boschi, Gabrielle, Rips, Richard, Scherrmann, Jean-Michel
Format: Article
Language:English
Subjects:
Animals
Biochemistry and metabolism
Biological and medical sciences
Brain - metabolism
Central nervous system
Colchicine
Colchicine - pharmacology
Delivery
Diffusion rate
Dose-Response Relationship, Drug
Fundamental and applied biological sciences. Psychology
Hippocampus
Hippocampus - drug effects
Male
Microdialysis
Neurotoxicity
Rats
Rats, Sprague-Dawley
Time Factors
Vertebrates: nervous system and sense organs
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Summary:The time courses of the colchicine delivery and diffusion rate in the brain were studied by microdialysis in the rat. Microdialysis allowed the exposure of the brain tissue to colchicine to be regulated, unlike a bolus injection. Colchicine was infused directly into the dorsal hippocampus at 40 ng/ml and 40 μg/ml, for 8 h. The amount of colchicine delivered to the brain and the diffusion rate from the probe were dose-dependent: colchicine diffusion into the brain was linear at 40 ng/ml but tended to plateau after 4 h at 40 μg/ml. The drug actually delivered with the higher dosage was only about 50% of that predicted from a constant diffusion. The total amount delivered at 40 ng/ml was 3.73 ± 0.14 ng and at 40 μg/ml, it was 2.06 ± 0.20,μg. Thus tissues surrounding the infusion site were saturated at high concentration and no more colchicine was diffused. Postmortem measurements of colchicine concentration in the forebrain confirmed these findings. Hence, the way in which colchicine is delivered to the brain is a critical factor for induction of its neurotoxic effects. These data open the way to a research on the correlation between local brain concentrations of colchicine and neurodegenerescence.
ISSN:0304-3940
1872-7972
DOI:10.1016/0304-3940(96)12374-0