Investigating the effects of a FAAH inhibitor in the laterodorsal tegmental nucleus using a new ex vivo mouse preparation

As part of the brainstem reticular activating system, the laterodorsal tegmentum (LDT) is a central player in
regulating sleep, arousal, and motivated behaviors including addiction. The neuronal lipids within the LDT that
could regulate neuronal activity and LDT signaling are not fully characterized due, in part, to the complication of
the presence of fatty acid amide hydrolases (FAAH). To determine the lipids in the LDT, mouse brain slices at
different stages of brain development (16, 26 and 66 days) were exposed ex vivo to the FAAH inhibitor oleyl
trifluoromethyl ketone (OTMK). Metabolomics and proteomic analyses were conducted on matched samples.
Metabolomics analysis revealed differences between OTMK treated and untreated LDT. Furthermore, a distinct
phenotype (proteomic profile) as a function of OTMK treatment was observed in LDT from adolescent (66 days)
mice indicating an effect of treatment with OTMK at later stages of brain development. Our data indicate that this
ex vivo preparation could facilitate screening of different FAAH inhibitors in mammalian tissues, and more
importantly, this preparation should allow a deeper characterization of global mass spectrometry-based omics
profiles within the LDT.