Alteration of neurotensin receptors in MPTP-treated mice

We examined the sequential changes in neurotensin receptors in the striatum and substantia nigra of mouse brains lesioned with 1-methyl-4-phenyl-1,2,3 ,6-tetrahydropyridine (MPTP) by receptor autoradiography, in comparison wit h the alterations in dopamine uptake sites. The mice received four intraper itoneal injections of MPTP (10 mg/kg) at l-h intervals and then the brains were analyzed at 6 h and 1, 3, 7, and 21 days after the treatments. [H-3]Ne urotensin and [H-3]mazindol were used to label neurotensin receptors and do pamine uptake sites, respectively. [H-3]Neurotensin binding was significant ly decreased in the striatum from 6 h to 21 days after MPTP treatment. In t he substantia nigra, pars reticulata also showed a significant decrease in [H-3]neurotensin binding from 3 to 21 days post-MPTP treatment. However, no significant change in [H-3]neurotensin binding was observed in the pars co mpacta even after 21 days. On the other hand, [H-3]mazindol binding was mar kedly decreased in the striatum and substantia nigra from 6 h to 21 days af ter MPTP treatment. These results indicate that neurotoxin MPTP can produce a severe decrease in neurotensin, receptors and dopamine uptake sites in t he striatum and substantia nigra of mice. Thus, our findings provide eviden ce that the dysfunction in neurotensin receptors may be involved in the deg enerative processes causing Parkinson's disease. (C) 1999 Elsevier Science Inc. All rights reserved.