NMDA antagonist effects on the development of L-DOPA behavioal sensitization in rats.

This study, which used an animal model of Parkinsonism, evaluated whether the N-methyl-D-aspartate (NMDA) antagonist MK-801 can prevent the development of L-3-4-dihydroxyphenylalanine ({l}-DOPA) sensitization. In separate groups, rats with unilateral 6-hydroxydopamine (6-OHDA) lesions were treated with saline, 25 mg/kg {l}-DOPA methyl ester, 0.1 mg/kg MK-801, or MK-801 plus {l}-DOPA once per day for 13 days beginning 18–20 hrs postoperatively, well before the onset of denervation supersensitivity. Following 14 days of withdrawal, all treatment groups were given a saline test and on the next day, an {l}-DOPA challenge test. Contralateral rotation, the behavioral index of denervation supersensitivity, emerged on Day 7 in both {l}-DOPA groups. However, on the {l}-DOPA challenge test, only the {l}-DOPA group showed enhanced contralateral rotations compared with a drug-naive group. In contrast, the MK-801 and MK-801/{l}-DOPA groups were indistinguishable from the drug-naive {l}-DOPA-treated rats. These findings indicate that although MK-801 treatment did not prevent the development of behavioral sensitization to the {l}-DOPA treatment, it did prevent its persistence following drug withdrawal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)