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

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http://hdl.handle.net/10138/314672

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Alitalo , O , Rantamäki , T & Huhtala , T 2020 , ' Digital autoradiography for efficient functional imaging without anesthesia in experimental animals : Reversing phencyclidine-induced functional alterations using clozapine ' , Progress in Neuro-Psychopharmacology & Biological Psychiatry , vol. 100 , 109887 . https://doi.org/10.1016/j.pnpbp.2020.109887

Title: Digital autoradiography for efficient functional imaging without anesthesia in experimental animals : Reversing phencyclidine-induced functional alterations using clozapine
Author: Alitalo, Okko; Rantamäki, Tomi; Huhtala, Tuulia
Contributor: University of Helsinki, Division of Pharmacology and Pharmacotherapy
University of Helsinki, Drug Research Program
Date: 2020-06-08
Language: eng
Number of pages: 8
Belongs to series: Progress in Neuro-Psychopharmacology & Biological Psychiatry
ISSN: 0278-5846
URI: http://hdl.handle.net/10138/314672
Abstract: Autoradiography (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 functional activity. Digital ARG produces viable data for the regional analysis of functional activity in a fraction of time required for film development. These results support the use of digital ARG in preclinical drug research, where high throughput and response linearity are preferred and use of sedation/anesthesia has to be avoided.
Subject: Autoradiography
Particle-counting system
Functional imaging
Glucose utilization
Schizophrenia
Drug development
CEREBRAL GLUCOSE-UTILIZATION
POSITRON-EMISSION-TOMOGRAPHY
REGIONAL BRAIN METABOLISM
ISOFLURANE ANESTHESIA
CHRONIC-SCHIZOPHRENIA
2-DEOXYGLUCOSE UPTAKE
ACTIVITY PATTERNS
MOUSE-BRAIN
BLOOD-FLOW
KETAMINE
3112 Neurosciences
317 Pharmacy
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