Antiparkinson-like effects of neurotensin in 6-hydroxydopamine lesioned rats

The aim of the present study was to examine the effects of neurotensin in an animal model of Parkinson's disease (PD). Bilateral administration of 6-OHDA in the medial forebrain bundle at the level of the posterolateral hypothalamus of rats resulted in the appearance of the 3 principal neurological signs of PD: hypokinesia, rigidity and tremor. These symptoms were accompanied by severe losses of dopamine and its main metabolites in terminal regions of well-known dopamine pathways. Norepinephrine concentrations were also decreased in several regions but to a lesser extent than dopamine. Intracerebroventricular administration of neurotensin, in doses ranging from 7.5 to 120.0 micrograms, resulted in dose related attenuations of both muscular rigidity and tremors of animals. However, hypokinesia, defined as decreased motor activity was not significantly affected by the peptide. Administration of 120.0 micrograms of [Ala]NT, an inactive analogue of neurotensin, failed to alter any of the 3 neurological signs. Together, these results reveal selective antiparkinson-like effects of neurotensin in an animal model. The theoretical significance of these findings is discussed.