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Volume 17, Number 18, Issue of September 15, 1997 pp. 6899-6907
Copyright ©1997 Society for NeuroscienceThe Dopamine Transporter: Comparative Ultrastructure of Dopaminergic Axons in Limbic and Motor Compartments of the Nucleus Accumbens
Received May 5, 1997; revised July 1, 1997; accepted July 1, 1997.
Melissa J. Nirenberg1, June Chan1, Alicia Pohorille1, Roxanne A. Vaughan2, George R. Uhl3, 4, Michael J. Kuhar5, and Virginia M. Pickel1 1 Department of Neurology and Neuroscience, Cornell University Medical College, New York, New York 10021, 2 Neuroscience and 3 Molecular Neurobiology Branches, National Institute on Drug Abuse, Baltimore, Maryland 21224, 4 Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, and 5 Neuroscience Division, Yerkes Regional Primate Center, Emory University, Atlanta, Georgia 30322
The dopamine transporter (DAT) regulates extracellular dopamine concentrations, transports neurotoxins, and acts as a substrate for cocaine reinforcement. These functions are known to differ in the limbic-associated shell and motor-associated core compartments of the nucleus accumbens (NAc). Previous studies have shown differential expression of DAT in the NAc shell and core but were limited in resolution to the regional level. Thus, it is not known whether there are differences in the amount, subcellular localization, or plasmalemmal targeting of DAT within individual dopaminergic axons in the two regions. We used high-resolution electron microscopic immunocytochemistry to investigate these possibilities. We show that in both the shell and core, DAT immunogold labeling is present in tyrosine hydroxylase-immunoreactive varicose axons that form symmetric synapses. Within these labeled axons, most DAT gold particles are located on extrasynaptic plasma membranes, but some are associated with intracellular membranes. Dopaminergic axons in the shell contain lower mean densities of both total DAT gold particles (per square micron) and plasmalemmal DAT gold particles (per micron) than those in the core. Within labeled axons in the NAc shell and core, however, there are no detectable differences in the subcellullar distribution of DAT or the percentage of total DAT gold particles that are located on plasma membranes. These studies are the first to examine and compare the subcellular localization of DAT in the NAc shell and core. As a result, they identify intrinsic, cell-specific differences in the expression of DAT within dopaminergic axons in these functionally distinct striatal compartments.
Key words: dopamine transporter; dopamine reuptake; immunogold; accumbens; striatum; cocaine; amphetamine
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