Dopamine transporter knock‐out mice are hypersensitive to 3‐nitropropionic acid‐induced striatal damage

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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.