A cannulation technique for frequent sampling of cerebrospinal fluid (CSF) in unanaesthetized freely moving rats is described. A permanent stainless steel cannula, constructed in such a way that no loss of CSF occurs, is placed into the rat's cisterna magna and fixed to the skull by anchoring screws and dental cement. A special CSF outflow opening of the cannula is connected to polyethylene tubing for CSF sampling. Amounts of 50–150 μl CSF can be collected repeatedly without any sign of disturbing the animal. The technique lends itself not only to pilot studies in which within a short period of time a large amount of CSF is wanted, but also to experiments in which physiological conditions are required
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