BEHAVIORAL AND NEUROCHEMICAL RECOVERY FROM PARTIAL 6-HYDROXYDOPAMINE LESIONS OF THE SUBSTANTIA-NIGRA IS BLOCKED BY DAILY TREATMENT WITH GLUTAMATE-RECEPTOR ANTAGONISTS MK-801 AND CPP

To determine whether glutamate plays a role in the recovery from lesio ns of the substantia nigra, measures of behavioral functioning and ext racellular levels of striatal dopamine (DA) were made after partial un ilateral 6-OHDA lesions in adult male rats. In experiments 1 and 2, an imals were treated on days 1-8 after lesioning with the noncompetitive NMDA receptor antagonist dizocilpine maleate (MK-801; 0.25 mg/kg, i.p .) or saline, and in experiment 3 with the competitive antagonist [(+/ -)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid (CPP; 1.0 mg/kg, i .p.) or saline. In experiment 1, behavior was assessed 3 and 8 d after lesioning before daily drug treatment; on days 9 and 10, basal extrac ellular DA and metabolites were measured in both striata using microdi alysis. in experiments 2 and 3, behavior was assessed on days 3 and 15 and microdialysis on days 16 and 17, 8-9 d post-termination of drug t reatments. On day 3, all animals turned ipsilateral to the lesion. On days 8 or 15, saline-treated animals showed no behavioral asymmetries, whereas MK-801- and CPP-treated animals turned ipsilaterally. in anta gonist-treated animals, basal levels of extracellular DA were lower on the lesioned side whether measured 9-10 or 16-17 d after lesioning, w hereas in saline-treated animals DA levels on the two sides did not di ffer. These results suggest that glutamate plays a role in the develop ment of compensatory changes in the DA neurons that accompany behavior al recovery from partial lesions of nigrostriatal DA system.