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Quantitative pharmacologic MRI: Mapping the cerebral blood volume response to cocaine in dopamine transporter knockout mice

Perles-Barbacaru, Teodora-Adriana and Procissi, Daniel and Demyanenko, Andrey V. and Hall, F. Scott and Uhl, George R. and Jacobs, Russell E. (2011) Quantitative pharmacologic MRI: Mapping the cerebral blood volume response to cocaine in dopamine transporter knockout mice. NeuroImage, 55 (2). pp. 622-628. ISSN 1053-8119. PMCID PMC3035982. https://resolver.caltech.edu/CaltechAUTHORS:20110119-091833009

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Abstract

The use of pharmacologic MRI (phMRI) in mouse models of brain disorders allows noninvasive in vivo assessment of drug-modulated local cerebral blood volume changes (ΔCBV) as one correlate of neuronal and neurovascular activities. In this report, we employed CBV-weighted phMRI to compare cocaine-modulated neuronal activity in dopamine transporter (DAT) knockout (KO) and wild-typemice. Cocaine acts to block the dopamine, norepinephrine, and serotonin transporters (DAT, NET, and SERT) that clear their respective neurotransmitters from the synapses, helping to terminate cognate neurotransmission. Cocaine consistently reduced CBV, with a similar pattern of regional ΔCBV in brain structures involved inmediating reward in both DAT genotypes. The largest effects (−20% to −30% ΔCBV) were seen in the nucleus accumbens and several cortical regions. Decreasing response amplitudes to cocaine were noted in more posterior components of the cortico-mesolimbic circuit. DAT KO mice had significantly attenuated ΔCBV amplitudes, shortened times to peak response, and reduced response duration in most regions. This study demonstrates that DAT knockout does not abolish the phMRI responses to cocaine, suggesting that adaptations to loss of DAT and/or retained cocaine activity in other monoamine neurotransmitter systems underlie these responses in DAT KO mice.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.neuroimage.2010.12.048DOIArticle
http://www.sciencedirect.com/science/article/B6WNP-51SFK01-1/2/f48d7504000c11a1999bc318f1ddd385PublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3035982/PubMed CentralArticle
ORCID:
AuthorORCID
Jacobs, Russell E.0000-0002-1382-8486
Additional Information:© 2010 Elsevier Inc. Received 17 May 2010; revised 15 December 2010; accepted 17 December 2010. Available online 23 December 2010. The authors thank Hargun Sohi and Thomas Ng for their technical assistance, Davit Janvelyan for helping with the AIR software, Guerbet Research (Aulnay-Sous-Bois, France) for providing the P904 contrast agent. This project was funded in part by the Beckman Institute, NIDA R01DA18184, and NCRR U24 RR021760 Mouse BIRN and by funding from the National Institute on Drug Abuse, Intramural Research Program (GRU, FSH).
Funders:
Funding AgencyGrant Number
Caltech Beckman InstituteUNSPECIFIED
National Institute on Drug AbuseR01DA18184
National Center for Research Resources (NCRR)U24 RR021760
Issue or Number:2
PubMed Central ID:PMC3035982
Record Number:CaltechAUTHORS:20110119-091833009
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20110119-091833009
Official Citation:Teodora-Adriana Perles-Barbacaru, Daniel Procissi, Andrey V. Demyanenko, F. Scott Hall, George R. Uhl, Russell E. Jacobs, Quantitative pharmacologic MRI: Mapping the cerebral blood volume response to cocaine in dopamine transporter knockout mice, NeuroImage, Volume 55, Issue 2, 15 March 2011, Pages 622-628, ISSN 1053-8119, DOI: 10.1016/j.neuroimage.2010.12.048.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:21805
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:10 Feb 2011 03:07
Last Modified:03 Oct 2019 02:29

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