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Preclinical contract research: animal models of neurological disorders:

Preclinical Parkinson's disease models (PD models)

For an in vitro assay of potential PD compounds, see the In Vitro Assays page.

         Rat (unilateral 6-OHDA lesion)

     Adult rats with this lesion exhibit several behavioral deficits, as well as show significant loss of both dopaminergic neurons in the substantia nigra and dopaminergic projections to the striatum on the lesioned side.  This model is known to be sensitive to test compounds that affect dopaminergic activity. 

 

         Mouse (MPTP lesion)

     This progressive-neuron-loss model of Parkinson’s disease uses repeated injections of low doses of the MPTP toxin, and multiple behavioral measures. 

For a description of this model [Click here] and for specific data on the effects of L-DOPA and nicotine in this model [Click here]

An acute high-dose of MPTP is also sometimes used with this model

For an example study [Click here]

       

Dyskinesia and tremor (mouse, rat)

     Current Parkinson's disease treatments that target dopamine receptors induce dyskinesias with extended use.  To test therapeutics that may reduce these dyskinesias, a mouse model is used that induces dyskinetic-like behaviors by prolonged treatment with 6-OHDA (click here for a description of this model [Smith et al., 2012]).

      Separate from dyskinesia, Parkinson's disease is characterized in part by the presence of a resting tremor, often "pill-rolling" but also tremulous jaw movements.  A rat model induces tremulous jaw movements (TJM) using pilocarpine, tetrabenazine, or a combination of drugs, and specifically measures the frequency of the jaw movements (click here for a description of this model [Collins et al., 2011]).  The latter model has characteristics of Parkinsonian tremor but is distinct from tardive dyskinesia.

 

For an additional description of this model [Click here]

 

         Marmoset MPTP lesion

     This is the only animal model of Parkinson’s disease that expresses L-DOPA-induced psychoses, as well as dyskinesia, in addition to the usual parkinsonian motor symptoms.  As the marmoset weighs much less than the macaque, the other common non-human primate model of PD, much less test drug is needed to evaluate efficacy.  No drug that has exhibited anti-Parkinsonian activity clinically has not also shown efficacy in this model.

(For an example study [Click here]).

 

 

 

 

 

 

 [Back to animal models list]

 


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