title: Relating Translational Neuroimaging and Amperometric Endpoints: Utility for Neuropsychiatric Drug Discovery.
abstract: Measures of neuronal activation are a natural and parsimonious translational biomarker to consider in the context of neuropsychiatric drug discovery studies. In this regard, functional neuroimaging using the BOLD fMRI technique is becoming more frequently employed to not only probe aberrant brain regions and circuits in disease, but also to assess the effects of novel pharmacological agents on these processes. In the ideal situation, these types of studies would first be conducted pre-clinically in rodents to confirm a measurable functional response on relevant brain circuits before seeking to replicate the findings in an analogous fMRI paradigm in humans. However, the need for animal immobilization during the scanning procedure precludes all but the simplest behavioural task-based paradigms in rodent BOLD fMRI. This chapter considers how in vivo oxygen amperometry may represent a viable and valid proxy for BOLD fMRI in freely moving rodents engaged in behavioural tasks. The amperometric technique and several examples of emerging evidence are described to show how the technique can deliver results that translate to pharmacological, event-related and functional connectivity variants of fMRI. In vivo oxygen amperometry holds great promise as a technique that may help to bridge the gap between basic drug discovery research in rodents and applied efficacy testing in humans.
authors.affiliation: In Vivo Pharmacology, Eli Lilly and Company, Erl Wood Manor, Sunninghill Road, Windlesham, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Li
authors.affiliation: Translational Imaging, Eli Lilly and Company, Indianapolis, IN, 46285, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Schwarz
authors.affiliation: In Vivo Pharmacology, Eli Lilly and Company, Erl Wood Manor, Sunninghill Road, Windlesham, UK. gilmour_gary@lilly.com.
authors.forename: Gary
authors.initials: G
authors.lastname: Gilmour
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D001931:Brain Mapping / Q000379:methods*; D055808:Drug Discovery; D059907:Functional Neuroimaging / Q000379:methods*; D007858:Learning / Q000502:physiology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D012201:Reward
keywords: BOLD signal; Functional connectivity; Magnetic resonance imaging; Oxygen amperometry; Pharmacological imaging; Reward-based learning