Abstract
Evidence suggests that dopamine is involved in the modulation of striatal excitotoxic processes. To further investigate this issue, we studied the effects of systemic 'low-dose' (total dose, 340 mg/kg in 7 days) 3-nitropropionic acid (3-NP) intoxication in dopamine transporter knock-out mice (DAT-/-) compared to wildtype (DAT+/+) mice. Systemic 'low-dose' 3-NP induced a significant impairment in a rotarod task only in DAT-/- mice. Histopathology also demonstrated a significant reduction of the striatal volume (-7%, P < 0.05), neuronal density (-12.5%, P < 0.001) and absolute number estimates of striatal neurons (-11.5%, P < 0.001) in DAT-/- compared to DAT+/+ mice, with increased glial activation, independent of the degree of succinate dehydrogenase inhibition. These findings strengthen the hypothesis for dopamine modulation of excitotoxicity within the nigrostriatal system.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Basal Ganglia Diseases / chemically induced
-
Basal Ganglia Diseases / metabolism*
-
Basal Ganglia Diseases / physiopathology
-
Cell Death / drug effects
-
Cell Death / physiology
-
Convulsants / pharmacology
-
Dopamine / metabolism*
-
Dopamine Plasma Membrane Transport Proteins
-
Dose-Response Relationship, Drug
-
Drug Tolerance / genetics*
-
Membrane Glycoproteins*
-
Membrane Transport Proteins / deficiency*
-
Membrane Transport Proteins / genetics
-
Mice
-
Mice, Knockout
-
Motor Activity / drug effects
-
Motor Activity / genetics
-
Neostriatum / injuries
-
Neostriatum / metabolism*
-
Neostriatum / physiopathology
-
Nerve Degeneration / chemically induced
-
Nerve Degeneration / metabolism
-
Nerve Degeneration / physiopathology
-
Nerve Tissue Proteins*
-
Neural Pathways / injuries
-
Neural Pathways / metabolism*
-
Neural Pathways / physiopathology
-
Neurotoxins / pharmacology
-
Nitro Compounds
-
Postural Balance / drug effects
-
Postural Balance / physiology
-
Propionates / pharmacology
-
Substantia Nigra / injuries
-
Substantia Nigra / metabolism*
-
Substantia Nigra / physiopathology
-
Up-Regulation / drug effects
-
Up-Regulation / physiology
Substances
-
Convulsants
-
Dopamine Plasma Membrane Transport Proteins
-
Membrane Glycoproteins
-
Membrane Transport Proteins
-
Nerve Tissue Proteins
-
Neurotoxins
-
Nitro Compounds
-
Propionates
-
Slc6a3 protein, mouse
-
3-nitropropionic acid
-
Dopamine