Digital autoradiography for efficient functional imaging without anesthesia in experimental animals: Reversing phencyclidine-induced functional alterations using clozapine

Publication date: Available online 12 February 2020Source: Progress in Neuro-Psychopharmacology and Biological PsychiatryAuthor(s): Okko Alitalo, Tomi Rantamäki, Tuulia HuhtalaAbstractAutoradiography (ARG) is a high-resolution imaging method for localization of radiolabeled biomarkers in ex vivo specimen. ARG using 2-deoxy-d-glucose (2-DG) method is used in to study drug actions on brain functional activity, as it provides results comparable to clinically used functional positron-emission tomography (PET). The requirement of slow analog detection methods and emerging advances in small animal PET imaging have, however, reduced the interest in ARG. In contrast to ARG, experimental animals need to be restrained or sedated/anesthetized for PET imaging, which strongly influence functional activity and thus complicate the interpretation of the results. Digital direct particle-counting ARG systems have gained attraction during the last decade to overcome the caveats of conventional ARG methods. Here we demonstrate that the well-established 2-DG imaging method can be adapted into use with contemporary digital detectors. This method readily and rapidly captures the characteristic effects of phencyclidine (5 mg/kg, i.p.), a dissociative agent targeting the NMDAR (N-methyl-d-aspartate receptor), on regional glucose utilization in the adult mouse brain. Pretreatment with antipsychotic drug clozapine (6 mg/kg, i.p.) essentially abolishes these effects of phencyclidine on brain functi...
Source: Progress in Neuro Psychopharmacology and Biological Psychiatry - Category: Psychiatry Source Type: research