L-DOPA is still the drug of choice to treat Parkinson's disease although adverse side effects appear after several years of treatment. These are thought to be the consequence of plastic re-arrangements of the nigrostriatal connections, such as sprouting of the dopaminergic terminals or post-synaptic changes. Pleiotrophin, a trophic factor that we have shown to be up-regulated in the striatum of parkinsonian rats after long-term L-DOPA treatment may play a role in these plastic changes. To determine whether one of the three known pleiotrophin receptors [N-syndecan, receptor protein tyrosine phosphatase type zeta beta (RPTP-zeta/beta) and anaplastic lymphoma kinase] might be implicated in these putative plastic effects, we quantified their expression levels by real-time RT-PCR in the striatum and mesencephalon of rats with partial lesions of the nigrostriatal pathway undergoing L-DOPA treatment. Both pleiotrophin and RPTP-zeta/beta expression was up-regulated in the striatum but not in the mesencephalon of lesioned rats and RPTP-zeta/beta expression was even further increased by L-DOPA. The levels of the RPTP-zeta/beta protein were also increased in the striatum of L-DOPA-treated lesioned rats. Immunofluorescence labeling showed the protein to be constitutively expressed in striatal medium spiny neurons, which are innervated by both the corticostriatal glutamatergic and nigrostriatal dopaminergic systems. RPTP-zeta/beta might therefore be implicated in the plastic changes triggered by L-DOPA treatment and might merit further study as a potential candidate for Parkinon's disease therapy.