Using awake animal imaging to fingerprint drugs for CNS liability: Risk of suicide?

Abstract

Awake animal imaging has become an important tool in preclinical drug discovery. Noninvasive ultra-high field, functional magnetic resonance imaging (fMRI) provides a window to the mind making it possible to image changes in brain activity across distributed, integrated neural circuits with high temporal and spatial resolution. Awake animal imaging offers the ability to record signal changes across the entire brain in seconds. When combined with the use of 3D segmented, annotated, brain atlases, and computational analysis, it is possible to reconstruct distributed, integrated neural circuits, or fingerprints of brain activity. These fingerprints can be used to characterize the activity and function of new psychotherapeutics in preclinical development and to study the neurobiology of integrated neural circuits controlling cognition and emotion. In this chapter, we briefly describe the methods used to image awake animals and its application toward the study of drugs with black box warnings for suicidal ideation and self-harm.