MPTP Model

In the MPTP model, MPTP is converted to MPP+ and selectively taken up into dopaminergic neurons, where it inhibits mitochondrial complex I. This results in degeneration of dopaminergic neurons and depletion of striatal dopamine, providing a model in which neurochemical endpoints can be used to assess the effects of an NCE. Both acute and sub-chronic dosing regimens can be used to support screening, efficacy and neuroprotection studies.

Acute MPTP administration (1 day, QID): striatal dopamine and metabolites
Striatal dopamine (DA) 4 and 7 days after acute MPTP: reduced versus saline (****). Striatal DOPAC 4 and 7 days after acute MPTP: reduced versus saline (* and ****).
Striatal HVA 4 and 7 days after acute MPTP: reduced versus saline (**). (DOPAC + HVA)/DA ratio 4 and 7 days after acute MPTP: increased versus saline (****), indicating increased dopamine turnover.

Striatal dopamine (DA) and its metabolites DOPAC and HVA, and the (DOPAC + HVA)/DA ratio, 4 and 7 days after acute MPTP. Open bars: saline; filled bars: MPTP.

Sub-chronic MPTP administration (5 days, BID): striatal dopamine and metabolites
Striatal dopamine (DA) 4 and 7 days after sub-chronic MPTP: reduced versus saline (** and ****). Striatal DOPAC 4 and 7 days after sub-chronic MPTP: reduced versus saline (****).
Striatal HVA 4 and 7 days after sub-chronic MPTP: reduced versus saline (****). (DOPAC + HVA)/DA ratio 4 and 7 days after sub-chronic MPTP: increased versus saline (**), indicating increased dopamine turnover.

Striatal dopamine (DA) and its metabolites DOPAC and HVA, and the (DOPAC + HVA)/DA ratio, 4 and 7 days after sub-chronic MPTP. Open bars: saline; filled bars: MPTP.

Acute and sub-chronic MPTP administration produces significant reductions in striatal dopamine (DA) and its metabolites DOPAC and HVA. Changes in the (DOPAC + HVA)/DA ratio provide an additional measure of dopamine turnover, with increases indicating increased dopaminergic turnover.