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Digital autoradiography for efficient functional imaging without anesthesia in experimental animals: Reversing
Okko Alitalo1, Tomi Rantamäki1, Tuulia Huhtala2
1Laboratory of Neurotherapeutics, Drug Research Program, Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Finland; SleepWell Research Program, Faculty of Medicine, University of Helsinki, Finland.
Progress in Neuro-Psychopharmacology & Biological Psychiatry
|February 17, 2020
Summary
Digital autoradiography (ARG) with 2-deoxy-d-glucose (2-DG) effectively images brain activity changes from drugs like phencyclidine and clozapine in mice, offering a faster alternative to traditional methods.
Area of Science:
- Neuroscience
- Medical Imaging
- Pharmacology
Background:
- Autoradiography (ARG) is a high-resolution imaging technique for localizing radiolabeled biomarkers in ex vivo samples.
- The 2-deoxy-d-glucose (2-DG) method in ARG studies drug effects on brain activity, comparable to clinical positron-emission tomography (PET).
- Conventional ARG methods face reduced interest due to slow detection and advances in small animal PET, which requires animal sedation that affects results.
Purpose of the Study:
- To adapt the 2-deoxy-d-glucose (2-DG) imaging method for use with contemporary digital ARG detectors.
- To evaluate the efficacy of digital ARG in capturing drug-induced changes in regional brain glucose utilization.
- To demonstrate the utility of digital ARG in preclinical drug research, avoiding sedation/anesthesia.
Main Methods:
- Utilized a digital direct particle-counting ARG system with the 2-deoxy-d-glucose (2-DG) method.
- Administered phencyclidine (5 mg/kg, i.p.) to adult mice to assess its effects on regional glucose utilization.
- Administered clozapine (6 mg/kg, i.p.) as a pretreatment to evaluate its effect on phencyclidine-induced changes.
Main Results:
- Digital ARG rapidly and effectively captured the effects of phencyclidine on regional glucose utilization in the adult mouse brain.
- Pretreatment with clozapine abolished the phencyclidine-induced alterations in brain functional activity.
- Digital ARG provided viable data for regional analysis in significantly less time compared to film development.
Conclusions:
- The 2-DG imaging method is successfully adapted for contemporary digital ARG detectors.
- Digital ARG is a viable, rapid, and effective tool for preclinical drug research, particularly for studying NMDAR antagonists.
- This method supports high-throughput analysis and response linearity while avoiding the need for animal sedation or anesthesia.
Keywords:
AutoradiographyDrug developmentFunctional imagingGlucose utilizationParticle-counting systemSchizophrenia
