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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Nyckelord

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

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)