Since its first applications, microdialysis has become increasingly popular to study brain function. The use of alternative in vivo procedures such as push-pull perfusion or voltammetry has remained constant or even declined during last years. A comparison between microdialysis and voltammetry reveals that microdialysis is applicable to most types of small molecules whereas the use of voltammetry is limited to easily oxidizable compounds such as catecholamines and serotonin. Moreover, micro-dialysis appears to be simple to use on a routine basis and can easily be applied to study freely moving animals.
Table 1 summarizes some of the advantages and limitations of microdialysis. Certainly, microdialysis is by no means a definitive method for the assessment of the active transmitter concentrations in the brain. Yet, it has a number of advantages over its predecessor, the push-pull perfusion, which have led to a more widespread use. The main limitations of microdialysis are the size of the probes and the tissue damage caused by their insertion. For certain applications, size may not be a problem (e.g., to assess the effects of drugs in large brain regions). However, the study of physiologically- or pharmacologically-induced changes of transmitters in small nuclei may pose some constraint because a larger proportion of neurones is damaged.
Finally, the low amount of certain neurotransmitters in brain dialysates makes it necessary to collect samples every 20 or 30 min, a time scale which is far from that of neuronal events. This may not be a problem in pharmacological studies because most drugs reach peak levels at a time compatible with the usual periods of sampling of 20 or 30 min. This enables to follow up drug-induced transmitter changes. However, microdialysis may not be suitable for the study of the effects of neuronal stimulation on transmitter release at a physiological time scale. Recent advances in the detection of very low concentration of certain transmitters with capillary electrophoresis have permitted a considerable shortening of the sampling periods. Yet, this is still far from the scale at which neuronal excitation or inhibition is associated to the release of a transmitter. It is hoped that future methodological and technical developments will overcome some of these limitations.
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