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

AbstractEvidence 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.

Auteurs Bordeaux Neurocampus