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Amphetamine-induced dopamine release in rat: Whole-brain spatiotemporal analysis with [11C]raclopride and positron emission tomography
Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.ORCID iD: 0000-0002-4501-4735
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.ORCID iD: 0000-0002-3731-3612
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
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2024 (English)In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 44, no 3, p. 434-445Article in journal (Refereed) Published
Abstract [en]

Whole-brain mapping of drug effects are needed to understand the neural underpinnings of drug-related behaviors. Amphetamine administration is associated with robust increases in striatal dopamine (DA) release. Dopaminergic terminals are, however, present across several associative brain regions, which may contribute to behavioral effects of amphetamine. Yet the assessment of DA release has been restricted to a few brain regions of interest. The present work employed positron emission tomography (PET) with [11C]raclopride to investigate regional and temporal characteristics of amphetamine-induced DA release across twenty sessions in adult female Sprague Dawley rats. Amphetamine was injected intravenously (2 mg/kg) to cause displacement of [11C]raclopride binding from DA D2-like receptors, assessed using temporally sensitive pharmacokinetic PET model (lp-ntPET). We show amphetamine-induced [11C]raclopride displacement in the basal ganglia, and no changes following saline injections. Peak occupancy was highest in nucleus accumbens, followed by caudate-putamen and globus pallidus. Importantly, significant amphetamine-induced displacement was also observed in several extrastriatal regions, and specifically in thalamus, insula, orbitofrontal cortex, and secondary somatosensory area. For these, peak occupancy occurred later and was lower as compared to the striatum. Collectively, these findings demonstrate distinct amphetamine-induced DA responses across the brain, and that [11C]raclopride-PET can be employed to detect such spatiotemporal differences.

Place, publisher, year, edition, pages
Sage Publications, 2024. Vol. 44, no 3, p. 434-445
Keywords [en]
Amphetamine, displacement, dopamine, imaging, receptor
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:umu:diva-216126DOI: 10.1177/0271678X231210128ISI: 001089209600001PubMedID: 37882727Scopus ID: 2-s2.0-85174906502OAI: oai:DiVA.org:umu-216126DiVA, id: diva2:1809957
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Swedish Research CouncilAvailable from: 2023-11-06 Created: 2023-11-06 Last updated: 2024-06-19Bibliographically approved

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Johansson, JarkkoEricsson, MadeleneAxelsson, Janaf Bjerkén, SaraVirel, AnaKaralija, Nina

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Johansson, JarkkoEricsson, MadeleneAxelsson, Janaf Bjerkén, SaraVirel, AnaKaralija, Nina
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Umeå Centre for Functional Brain Imaging (UFBI)Diagnostic RadiologyUmeå Centre for Molecular Medicine (UCMM)Radiation PhysicsDepartment of Integrative Medical Biology (IMB)Neurosciences
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Journal of Cerebral Blood Flow and Metabolism
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