Distribution of norepinephrine transporters in the non-human primate brain

Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
Neuroscience (Impact Factor: 3.36). 02/2006; 138(2):703-14. DOI: 10.1016/j.neuroscience.2005.11.033
Source: PubMed


Noradrenergic terminals in the central nervous system are widespread; as such this system plays a role in varying functions such as stress responses, sympathetic regulation, attention, and memory processing, and its dysregulation has been linked to several pathologies. In particular, the norepinephrine transporter is a target in the brain of many therapeutic and abused drugs. We used the selective ligand [(3)H]nisoxetine, therefore, to describe autoradiographically the normal regional distribution of the norepinephrine transporter in the non-human primate central nervous system, thereby providing a baseline to which alterations due to pathological conditions can be compared. The norepinephrine transporter in the monkey brain was distributed heterogeneously, with highest levels occurring in the locus coeruleus complex and raphe nuclei, and moderate binding density in the hypothalamus, midline thalamic nuclei, bed nucleus of the stria terminalis, central nucleus of the amygdala, and brainstem nuclei such as the dorsal motor nucleus of the vagus and nucleus of the solitary tract. Low levels of binding to the norepinephrine transporter were measured in basolateral amygdala and cortical, hippocampal, and striatal regions. The distribution of the norepinephrine transporter in the non-human primate brain was comparable overall to that described in other species, however disparities exist between the rodent and the monkey in brain regions that play a role in such critical processes as memory and learning. The differences in such areas point to the possibility of important functional differences in noradrenergic information processing across species, and suggest the use of caution in applying findings made in the rodent to the human condition.

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Available from: Thomas J R Beveridge, Aug 20, 2014
    • "NET has been shown to be involved in various psychiatric and behavioral disorders, such as attention deficit hyperactivity disorder (ADHD) (Bymaster et al., 2002, Spencer et al., 2002), substance abuse and depression (Klimek et al., 1997), and AD (Herrmann et al., 2004) . NET imaging with PET is challenged due to the widespread distribution of NET in the brain and the lower contrast in density between NET-poor and NET-rich regions (Smith et al., 2006). Of the tracers developed so far[ 11 C]MRB has shown improved specific binding (Logan et al., 2007, Gallezot et al. 2010).[ "
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    ABSTRACT: Objective: Alzheimer's disease (AD) is a neurodegenerative disease characterized by Aβ plaques in the brain. The aim of this study was to evaluate the effectiveness of a novel radiotracer, 4-[(11) C]methylamino-4'-N,N-dimethylaminoazobenzene ([(11) C]TAZA), for binding to Aβ plaques in postmortem human brain (AD and normal control (NC)). Methods: Radiosyntheses of [(11) C]TAZA, related [(11) C]Dalene ((11) C-methylamino-4'-dimethylaminostyrylbenzene) and reference [(11) C]PIB were carried out by using [(11) C]methyltriflate prepared from [(11) C]CO2 and purified using HPLC. In vitro binding affinities were carried out in human AD brain homogenate with Aβ plaques labeled with [(3) H]PIB. In vitro autoradiography studies with the three radiotracers were performed on of hippocampus of AD and NC brains. PET/CT studies were carried out in normal rats to study brain and whole body distribution. Results: The 3 radiotracers were produced in high radiochemical yields (>40%) and had specific activities >37 GBq/μmol. TAZA had an affinity, Ki= 0.84 nM and was to be 5 times more potent than PIB. [(11) C]TAZA bound specifically to Aβ plaques present in AD brains with grey matter to white matter ratios >20. [(11) C]TAZA was displaced by PIB (>90%), suggesting similar binding site for [(11) C]TAZA and [(11) C]PIB. [(11) C]TAZA exhibited slow kinetics of uptake in the rat brain and whole body images showed uptake in interscapular brown adipose tissue (IBAT). Binding in brain and IBAT were affected by pre-injection of atomoxetine, a norepinephrine transporter blocker. Conclusion: [(11) C]TAZA exhibited high binding to Aβ plaques in human AD hippocampus. Rat brain kinetics were slow and peripheral binding to IBAT needs to be further evaluated. This article is protected by copyright. All rights reserved.
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    • "It is also possible that different levels of accumulated NA taken up into presynaptic terminals depend on NAT activity. In the brain stem, a strong radiolabeled density of the NAT selective ligand[3H]nisoxetine has been observed in the LC (100%), DMV (35%) and NTS (21%), attaining only 10-12% in the 12N and IO, containing only NA axons[10]. It is known that NTS receives NA inputs from caudally located DVC[4,21,43,59], AP[60]and ventromedially located A1 cell region[61]. "

    Full-text · Article · Jan 2015
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    • "Furthermore, the connectivity patterns of the prefrontal cortex as well as other brain regions of nonhuman primates are highly homologous to those of humans (Ongur et al., 2003). Other advantages of nonhuman primates include similarities in the anatomy and physiology of dopaminergic (Gonzalez-Hernandez et al., 2004; Sanchez-Gonzalez et al., 2005) and noradrenergic systems (Smith et al., 2006), as well as the hypothalamic–pituitary– adrenal axis (e.g. Morgan et al., 2000). "

    Full-text · Dataset · Aug 2014
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