For CNS drug development, ex vivo receptor occupancy (RO) offers a simple yet powerful way to monitor the interaction of drug candidates with their targets in the brain after peripheral administration. A drug candidate has to possess good 'drug-like' properties to achieve significant brain occupancy of its target, which makes ex vivo RO an efficient filter to eliminate inferior compounds. Beta-imaging technology (developed by Biospace, Fr) has significantly shortened the time needed for such assessment (hours vs weeks for tritiated ligands), which makes it possible to exploit ex vivo RO as a screening tool.

Ex vivo RO can also be used to better understand the PK-PD relationship for drug candidates (e.g., plasma drug level vs target occupancy vs behavior effect), to assist in translational tool development (PET tracer) and dose selection in clinical trials.

Quantitative Western blott and qRT-PCR are useful technologies for quick examination of gene expression changes in protein and mRNA levels in various genetically modified and in drug treated animals. Western blott is also useful to monitor post-translational modifications. They can be employed in understanding the mechanism of actions for the drug candidates and to establish PK/PD relation ships for targets for which radioligands are not available.

Histology is used to characterize gross morphological changes such as lesions and neurodegeneration, or to measure structure volume and cell count. Immunohistochemistry can be used for neurochemical cell phenotyping, for the localization of neurons containing certain peptides, enzymes or receptors and for measurement of synaptic markers. Immunohistochemistry can also be used to measure neuronal activity. Using different antibodies, more than one protein can be visualized on a single section to provide information on co-expression and localization.

Neuronal death by apoptosis and necrosis, and cell proliferation in the adult mouse brain, can be measured by TUNEL staining, silver staining, and BrdU labeling, respectively.

PsychoGenics can offer the latest techniques in neuromorphology, including brain fixation, sectioning, and staining together with sample digitalization and analysis, through the close relationships we have with CROs specialized in Histology and Neuromorphology services.