MPTP A nimal M odel of P arkinsonism: D opamine C ell D eath or O nly T yrosine H ydroxylase I mpairment? – A S tudy U sing PET I maging, A utoradiography, and I mmunohistochemistry in the C at

Summary Aims 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine ( MPTP ) is a neurotoxin widely used to produce experimental models of Parkinson's disease in laboratory animals. It is believed to cause a selective destruction of substantia nigra dopamine neurons, mainly based on a large reduction of tyrosine hydroxylase ( TH ), the catecholamine's synthesizing enzyme. Unlike Parkinson's disease in humans, however, all animal models are able to recover more or less rapidly from the MPTP induced Parkinsonian syndrome. This raises the question as whether MPTP causes a cell death with a decrease in dopamine transporter or a simple impairment of TH . Methods To respond to this question, we quantified in a cat model of Parkinson's disease ( MPTP 5 mg/kg i.p. during 5 days) the dopamine transporter using positron emission tomography (PET) imaging and autoradiography of [ 11 C] PE 2I and compared the data with the TH ‐immunoreactivity. Results We found no changes in [ 11 C] PE 2I PET binding either 5 or 26 days after MPTP treatment when compared to baseline levels. Similarly, there were no significant changes in [ 11 C] PE 2I autoradiographic binding in the cat brain one week after MPTP treatment. In sharp contrast, MPTP treated cats exhibited severe Parkinson‐like motor syndrome during the acute period with a marked decrease in TH ‐immunoreactivity in the striatum. Conclusion These data suggest that MPTP toxicity impairs efficiently TH and that such an effect is not necessarily accompanied by significant reduction of dopamine transporter seen with in vitro or in vivo [ 11 C] PE 2I binding.