Partial ablation of mu-opioid receptor rich striosomes produces deficits on a motor-skill learning task

Abstract Basal ganglia striosomes, or patches, are rich in mu opioid receptors (MOR) and form a three-dimensional labyrinth of cells that extend throughout the mid- and anterior striatum in mice. Though previous studies have suggested that striosomes could affect drug-induced motor output in rodents...

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Bibliographic Details
Published in:Neuroscience 2009-09, Vol.163 (1), p.109-119
Main Authors: Lawhorn, C, Smith, D.M, Brown, L.L
Format: Article
Language:English
Subjects:
Analgesics, Opioid
Animals
Biological and medical sciences
Cell Count
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Denervation
Down-Regulation - drug effects
Down-Regulation - physiology
Dyskinesia, Drug-Induced - metabolism
Dyskinesia, Drug-Induced - physiopathology
Fundamental and applied biological sciences. Psychology
Huntington's disease
Immunotoxins
Learning - physiology
Learning Disorders - chemically induced
Learning Disorders - metabolism
Learning Disorders - physiopathology
Male
Medical sciences
Mice
motor
Motor Skills - physiology
mu opioid receptor
Neostriatum - cytology
Neostriatum - metabolism
Nerve Degeneration - chemically induced
Nerve Degeneration - metabolism
Nerve Degeneration - physiopathology
Neurology
Neurons - cytology
Neurons - metabolism
Neuropsychological Tests
Opioid Peptides
Receptors, Opioid, mu - metabolism
Ribosome Inactivating Proteins, Type 1
rotarod
striatum
striosomes
Vertebrates: nervous system and sense organs
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Summary:Abstract Basal ganglia striosomes, or patches, are rich in mu opioid receptors (MOR) and form a three-dimensional labyrinth of cells that extend throughout the mid- and anterior striatum in mice. Though previous studies have suggested that striosomes could affect drug-induced motor output in rodents, the functional role of these compartmentalized MOR-rich striosomes is not well understood. To investigate any relationship between the striosomes and motor behavior we used the toxin dermorphin-saporin (DS) to selectively ablate MOR-rich striosomal cells. FVB mice were bilaterally infused with DS in the midstriatum alone or in the mid- and anterior striatum, and were tested on three motor tasks and in an open field. Two volume measurement procedures and stereological cell counts were used to confirm the induced pathology. Mice that received DS injections showed significantly smaller volumes (−26% to −44%) and fewer cells (−30% to −49%) in the striosome compartment compared to mice that received control injections of saline or saporin. Striosome pathology was greatest in the dorsolateral striatum. The extrastriosomal matrix was not significantly affected, resulting in an imbalance in the ratio of striosome-to-matrix cells. Behaviorally, toxin injections caused deficits on an accelerating rotarod task and the deficit was worse in mice that received mid and anterior injections than those that received midstriatal injections alone. However, DS-injected mice did not differ from control mice on other motor tasks. We conclude that the MOR-rich cells of the striosomes are necessary for optimal rotarod performance, including learning and/or improvement on the task.
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2009.05.021