Do neurotransmitters sampled by brain microdialysis reflect functional release?

Brain microdialysis is an invasive sampling technique and will always cause damage to nervous tissue. For proper interpretation of the results, possib le sources of interference need to be identified. The present review discus ses the possible artefacts of the microdialysis technique and evaluates met hods used to investigate the possible neuronal origin of the sampled transm itters. Various neurotransmitter systems that are currently sampled by brain microd ialysis are critically evaluated here. Three criteria to validate the neuro nal origin of transmitters are discussed: 1. TTX- and calcium-dependency, 2. the detection of autoreceptors, and 3. the outcome of behavioural studies. The question whether neurotransmitters sampled by the brain microdialysis t echnique reflect functional release can be positively answered in case of d opamine, noradrenaline, serotonin and acetylcholine. However, in the case o f glutamate and GABA, the relationship between neuronal release and dialysa te content is not convincingly demonstrated. It is likely that synaptic tra nsmission of glutamate and GABA is very strictly compartmentalized, and as a result, these amino acids can hardly leak out of the synaptic cleft into the extracellular space where the dialysis probe samples. (C) 1999 Elsevier Science B.V. All rights reserved.