Modified microdialysis probe for sampling extracellular fluid and administering drugs in vivo

In vivo microdialysis provides an important new tool for investigating changes in extracellular fluid levels of endogenous compounds in vivo. Delivery of drugs via the microdialysis probe can be used to study local release and metabolism of neurotransmitters, but the dialysis membrane limits diffusion of substances between the perfusate and the extracellular fluid. Thus there may be considerable delay in responses, drug concentrations at the effector sites are less than those in the probe, and high-molecular-weight substances cannot traverse the membrane at all. This report describes a simple modification of commercially available microdialysis probes. A cannula is glued to the external surface of the probe. When glycine was administered via the cannula into the striatum of conscious rats, increments in microdialysate concentrations of dopamine were at least 10 times greater than when glycine was administered via the dialysis fluid in the probe. The threshold glycine dose for behavioral (turning) effects was also decreased by approximately 60-fold, and the time to the peak neurochemical and behavioral effects was markedly decreased. The modified probe did not destroy local catecholaminergic cells, as indicated by tyrosine hydroxylase immunofluorescence. Use of the modified microdialysis probe should facilitate pharmacological and neuroendocrine studies in behaving animals.