title: Subcellular distribution and plasticity of neurokinin-1 receptors in the rat substantia nigra and ventral tegmental area.
abstract: Neurokinin-1 receptors show activity-dependent changes in their surface distributions that are critical in spinal pain mechanisms, and also may play an important role in the motor and affective behaviors influenced by dopaminergic projections from the substantia nigra and ventral tegmental area. To determine the relevant sites for neurokinin-1 receptor activation in these midbrain regions, we examined the electron microscopic immunolabeling of neurokinin-1 receptors and the dopamine-synthesizing enzyme, tyrosine hydroxylase in normal rats. We also examined whether neurokinin-1 receptor distributions in one or both regions are affected by (1) startle-evoking intense auditory stimulation or (2) acute administration of apomorphine, a dopamine D1/D2 agonist that enhances startle while paradoxically reducing the prepulse inhibition produced by low intensity conditioning stimuli in rat models of schizophrenia. In each region, neurokinin-1 immunogold was located on the plasma membrane and endomembranes of somatodendritic profiles with or without tyrosine hydroxylase. As compared with controls, animals receiving intense auditory stimulation either alone or together with smaller low intensity prepulses showed a significant increase in neurokinin-1-plasmalemmal labeling in non-dopaminergic dendrites of both regions, and a reduction in this labeling in dopaminergic dendrites of the ventral tegmental area. Both effects were diminished following apomorphine administration. In absence of the intense auditory stimulation, however, apomorphine increased neurokinin-1-immunogold particles on the plasma membrane of the non-dopaminergic dendrites exclusively in the substantia nigra. Our results are the first to show that neurokinin-1 receptors have plasmalemmal distributions in dopaminergic and non-dopaminergic neurons that can be differentially modified by startle-evoking auditory stimulation. They suggest that while apomorphine can independently affect neurokinin-1 receptor trafficking in substantia nigra motor circuits, its effects on neurokinin-1 receptor distributions in the ventral tegmental area are exclusively dependent on sensory activation.
authors.affiliation: Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 411 East 69th Street, KB 410, New York, NY 10021, USA.
authors.forename: A
authors.initials: A
authors.lastname: Lessard
authors.forename: V M
authors.initials: VM
authors.lastname: Pickel
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D008297:Male; D016253:Microscopy, Immunoelectron; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000378:metabolism*; D013216:Reflex, Startle / Q000502:physiology; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018491:Dopamine Agonists; D018040:Receptors, Neurokinin-1; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine; D004298:Dopamine