In many mouse strains, notably the C57BL6, the systemic administration of MPTP results in a degeneration of the nigrostriatal DA system, the magnitude of which may be titrated by MPTP dose and dose regimen. Intervivo Solutions has experience of various MPTP protocols to offer graded depletions and the ability to assess endpoints at the behavioural, biochemical and anatomical level. This ability to titrate the extent of nigrostriatal DA depletion provides multiple opportunities to study the effects of an NCE against a variety of endpoints in this model.
Validation Data: Effect of MPTP dose on indices of striatal DA function
MPTP was administered under a regimen of either 3 x IP Vehicle injections (Control), 2 x IP MPTP injections or 3 x IP MPTP injections. After 14 days striatal tissue was harvested and analysed either using 125I-RTI121 a high affinity ligand for the Dopamine transporter, or measuring Dopamine content from striatal tissue. Both measures can be quantified allowing assessment of an NCE against each measure.
In the rat, the systemic injection of rotenone results in a variety of behavioural, biochemical and histopathological changes which bear parallels with changes in Parkinson’s Disease. Together these measures provide multiple endpoints to assess the effect of an NCE in this model.
Validation Data: Effect of Rotenone dose on indices of neurological function
A 10-12 daily regimen of rotenone (2.75 – 3 mg/kg IP) produces significant effects on tasks of neurological function The most robust changes are measured using rearing in open field, postural instability and beam walking. Tremor, hypolocomotion, catalepsy are inconsistently affected by rotenone treatment.