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Reward circuitry is perturbed in the absence of the serotonin transporter

Bearer, Elaine L. and Zhang, Xiaowei and Janvelyan, Davit and Boulat, Benoit and Jacobs, Russell E. (2009) Reward circuitry is perturbed in the absence of the serotonin transporter. NeuroImage, 46 (4). pp. 1091-1104. ISSN 1053-8119. PMCID PMC2693299.

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The serotonin transporter (SERT) modulates the entire serotonergic system in the brain and influences both the dopaminergic and norepinephrinergic systems. These three systems are intimately involved in normal physiological functioning of the brain and implicated in numerous pathological conditions. Here we use high-resolution magnetic resonance imaging (MRI) and spectroscopy to elucidate the effects of disruption of the serotonin transporter in an animal model system: the SERT knock-out mouse. Employing manganese-enhanced MRI, we injected Mn^(2+) into the prefrontal cortex and obtained 3D MR images at specific time points in cohorts of SERT and normal mice. Statistical analysis of co-registered datasets demonstrated that active circuitry originating in the prefrontal cortex in the SERT knock-out is dramatically altered, with a bias towards more posterior areas (substantia nigra, ventral tegmental area, and Raphé nuclei) directly involved in the reward circuit. Injection site and tracing were confirmed with traditional track tracers by optical microscopy. In contrast, metabolite levels were essentially normal in the SERT knock-out by in vivo magnetic resonance spectroscopy and little or no anatomical differences between SERT knock-out and normal mice were detected by MRI. These findings point to modulation of the limbic cortical–ventral striatopallidal by disruption of SERT function. Thus, molecular disruptions of SERT that produce behavioral changes also alter the functional anatomy of the reward circuitry in which all the monoamine systems are involved.

Item Type:Article
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URLURL TypeDescription CentralArticle
Jacobs, Russell E.0000-0002-1382-8486
Additional Information:© 2009 Elsevier Inc. Received 13 October 2008; revised 10 March 2009; accepted 11 March 2009. Available online 20 March 2009. We thank Mike Tyszka at Caltech for creation and implementation of the DTI routines; and Cornelius Hojatkashani, Ilya Eckstein, Boris Gutman, Natasha Lepore, Igor Yanovsky and Mubeena Mirza at the Laboratory for NeuroImaging at UCLA for invaluable assistance with LONI pipeline and TBM analysis. The project was funded in part by the Beckman Institute, NIH NIGMS GM47368, NINDS NS046810, P20 RR018757 (E.L.B.), NIDA R01DA18184, and NCRR U24 RR021760 Mouse BIRN (R.E.J.).
Funding AgencyGrant Number
Caltech Beckman InstituteUNSPECIFIED
National Institute of Neurological Disorders and Stroke (NINDS)NS046810
National Institute of Neurological Disorders and Stroke (NINDS)P20 RR018757
National Institute on Drug AbuseR01DA18184
National Center for Research Resources (NCRR)U24 RR021760
Subject Keywords:Serotonin transporter; Knock-out; Manganese enhanced MRI; Synaptic transmission; Transport; Morphometry; Statistical parametric mapping; DTI; MRS
Issue or Number:4
PubMed Central ID:PMC2693299
Record Number:CaltechAUTHORS:20090519-160159475
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Official Citation:Bearer, Elaine L., Zhang, Xiaowei, Janvelyan, Davit, Boulat, Benoit, Jacobs, Russell E., Reward circuitry is perturbed in the absence of the serotonin transporter, NeuroImage (2009), doi:10.1016/j.neuroimage.2009.03.026
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:14271
Deposited By: Jason Perez
Deposited On:18 Sep 2009 23:04
Last Modified:03 Oct 2019 00:48

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