Microdialysis is a time-honored technique for measuring levels of molecules in the extracellular space from specific brain regions in awake, freely behaving rodents. Tiny, specialized probes with membranes that have various pore sizes (depends on the molecule being collected) are stereotaxically inserted into specific brain regions or compartments where dialysate can be collected from continuously for up to 48 h.
We commonly measure neurotransmitter levels such as the monoamines (dopamine, noradrenaline, serotonin and their metabolites), acetylcholine, histamine, glutamate, and GABA. Other molecules that can be collected and measured are amino acids such as serine and cysteine, immune factors including some antibodies, kynurenines, and even some proteins. Exogenous compounds (test articles) and their metabolites can be collected and measured to ensure that therapies are reaching important brain regions at appropriate concentrations.
PGI performs multiple types of microdialysis studies. We can collect from a single brain region (single-probe) or from two different regions simultaneously (dual-probe) in rats or mice. We offer capabilities for PK/PD studies, quantitative microdialysis, retro-microdialysis, and push-pull microdialysis for larger molecules (i.e. peptides).
Samples are analyzed by our expert bioanalyses team using cutting edge techniques including UPLC-MSMS, radioimmunoassay assay, ELISA, and multiplex immunoassays.
Single and Dual-Probe Microdialysis for Neurotransmitters Assessment
Striatal Dopamine Modulation
Dose-related effects on extracellular striatal dopamine levels by ketamine (left panel) and amphetamine (right panel). Samples were collected in freely moving male Sprague Dawley, 250-300g, n=10/group. *=p<0.05, **=p<0.01
Acetylcholine Modulation in Dual-Probe Microdialysis
Acetylcholine: Probe 1 – prefrontal cortex
Acetylcholine: Probe 2 – hippocampus
Effects of Donepezil on extracellular acetylcholine levels in microdialysates collected from prefrontal cortex and hippocampus of freely moving rats by dual probe microdialysis. Sprague Dawley rats, male, 250-300g, n=10/group. *=p<0.05
Quantitative Microdialysis
Quantitative microdialysis studies are performed for pharmacokinetic measurements of compound concentrations (free fraction) in the extracellular space.
Concentrations (free fraction) following two doses of Compound A in the extracellular space of the brain in mice using quantitative microdialysis techniques.
