Hypertrophy of the medial globus pallidus in 6-hydroxydopamine-lesioned rats treated with levodopa

The motor effects of levodopa, evidenced by rotation behavior, became enhanced upon intermittent administration in rats with unilateral lesions of the nigrostriatal dopamine pathway by 6-hydroxydopamine (6-OHDA). However, the mechanisms of this behavioral sensitization, which is regarded to be analogous to levodopa-induced dyskinesias (LIDs) in patients with Parkinson's disease (PD), remain unknown. The fact that pallidotomy dramatically improves LIDs indicates that the medial globus pallidus (MGP) plays an important role in the development of LIDs. We found hypertrophy of the MGP in 6-OHDA-lesioned rats treated with levodopa twice daily for 2 weeks. The rats showed marked behavioral sensitization to levodopa. Furthermore, coadministration of 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT) with levodopa attenuated this hypertrophy together with prevention of the sensitization. These results suggest that this hypertrophy is an essential pathological change in the rodent model of LIDs. (C) 2003 Elsevier Science B.V. All rights reserved.