Monitoring extracellular glutamate in the rat brain by microdialysis and microsensors: pharmacological applications

PhD ceremony: Ms. M. Evering-van der Zeyden, 16.15 uur, Academiegebouw, Broerstraat 5, Groningen

Title: Monitoring extracellular glutamate in the rat brain by microdialysis and microsensors: pharmacological applications

Promotor(s): prof. B.H.C. Westerink

Faculty: Mathematics and Natural Sciences

The aim of the thesis of Miranda Evering-van der Zeyden was to investigate the origin of extracellular glutamate as detected by microdialysis or microsensors in the brain of the rat. Extracellular L-glutamate, an important and abundant excitatory neurotransmitter in the brain, is believed to be derived from both glial and synaptic sources.

First it she has investigated whether NMDA glutamate receptors localized on the somatodendritic sites of mesolimbic dopamine neurons can be used as a functional NMDA model. To that end a dual-probe microdialysis system was used. The NMDA receptors localized on dopamine neurons in the ventral tegmental area (VTA) were influenced by infusing glutamatergic compounds and the activity of these neurons was determined by recording dopamine in the ipsilateral nucleus accumbens (NAc). Effect of glutamatergic excitation was clearly detectable as infusions of NMDA increased dopamine levels to about 150% of controls. However, the model displays a limited sensitivity when a decrease in NMDA-receptor activity needs to be detected

Next the dual-probe model was used by Evering-van der Zeyden to apply glutamatergic pharmacological active compounds to dopamine neurons in the VTA. Her results of these experiments displayed a clear mismatch between the extracellular levels of glutamate, detected in microdialysis samples of the VTA, and the activity of dopaminergic cells in the VTA as measured by dopamine release in the NAc. These observations suggest that care should be taken to relate glutamate in microdialysates to ‘neuronal glutamatergic activity’ in the brain. However, during certain pharmacological conditions, a minor part of glutamate sampled by microdialysis, might be directly related to synaptic events.