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Partial depletion of dopamine in substantia nigra impairs motor performance without altering striatal dopamine neurotransmission

Artikel i vetenskaplig tidskrift
Författare Daniel Andersson
Hans Nissbrandt
Filip Bergquist
Publicerad i European Journal of Neuroscience
Volym 24
Nummer/häfte 2
Sidor 617-624
ISSN 0953-816X
Publiceringsår 2006
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi
Sidor 617-624
Språk en
Länkar dx.doi.org/10.1111/j.1460-9568.2006...
Ämnesord Adrenergic Uptake Inhibitors, pharmacology, Animals, Corpus Striatum, metabolism, physiopathology, Dendrites, metabolism, secretion, Disease Models, Animal, Dopamine, deficiency, secretion, Extracellular Fluid, drug effects, metabolism, Female, Motor Activity, physiology, Movement, physiology, Movement Disorders, metabolism, physiopathology, Neural Pathways, metabolism, physiopathology, Parkinsonian Disorders, metabolism, physiopathology, Presynaptic Terminals, metabolism, secretion, Rats, Rats, Sprague-Dawley, Substantia Nigra, metabolism, physiopathology, Synaptic Transmission, physiology, Tetrabenazine, pharmacology, Vesicular Monoamine Transport Proteins, antagonists & inhibitors, metabolism
Ämneskategorier Farmakologi, Experimentell hjärnforskning

Sammanfattning

Previous data indicate that the release of somatodendritic dopamine in substantia nigra influences motor activity and coordination, but the relative importance of somatodendritic dopamine release vs. terminal striatal dopamine release remains to be determined. We utilized simultaneous measurement of dopamine neurotransmission by microdialysis and motor performance assessment by rotarod test to investigate the effects of local dopamine depletion in rats. The vesicular monoamine transporter inhibitor tetrabenazine (100 µm) was administered locally in substantia nigra as well as in striatum. Nigral tetrabenazine administration decreased nigral dopamine dialysate concentrations to 7% of baseline and whole-tissue dopamine content by 60%. Nigral dopamine depletion was associated with a reduction in motor performance to 73 ± 6% of pretreatment value, but did not alter dialysate dopamine concentrations in the ipsilateral striatum. Striatal tetrabenazine administration decreased striatal dopamine dialysate concentrations to 5% of baseline and doubled the somatodendritic dopamine response to motor activity, but it was not associated with changes in motor performance or dopamine content in striatal tissue. Simultaneous treatment of substantia nigra and striatum reduced motor performance to 58 ± 5% of the pretreatment value. The results of this study indicate that partial depletion of nigral dopamine stores can significantly impair motor functions, and that increased nigral dopamine release can counteract minor impairments of striatal dopamine transmission.

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