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Dopamine transporter knock‐out mice are hypersensitive to 3‐nitropropionic acid‐induced striatal damage
Author(s) -
Fernagut PierreO.,
Diguet Elsa,
Jaber Mohamed,
Bioulac Bernard,
Tison François
Publication year - 2002
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2002.02047.x
Subject(s) - dopamine transporter , dopamine , excitotoxicity , medicine , endocrinology , chemistry , striatum , transporter , neuroscience , pharmacology , biology , dopaminergic , biochemistry , glutamate receptor , receptor , gene
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.