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Volume 16, Number 16, Issue of August 15, 1996 pp. 5216-5224
Copyright ©1996 Society for Neuroscience

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

Received Jan. 31, 1996; revised May 16, 1996; accepted May 30, 1996.

Adriana Emmi, Heshmat Rajabi, and Jane Stewart

Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, Montréal, Québec, Canada H3G 1M8

To determine whether glutamate plays a role in the recovery from lesions of the substantia nigra, measures of behavioral functioning and extracellular levels of striatal dopamine (DA) were made after partial unilateral 6-OHDA lesions in adult male rats. In experiments 1 and 2, animals 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 3-[(±)-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 extracellular DA and metabolites were measured in both striata using microdialysis. 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 treatments. 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 antagonist-treated animals, basal levels of extracellular DA were lower on the lesioned side whether measured 9-10 or 16-17 d after lesioning, whereas in saline-treated animals DA levels on the two sides did not differ. These results suggest that glutamate plays a role in the development of compensatory changes in the DA neurons that accompany behavioral recovery from partial lesions of nigrostriatal DA system.

Key words: substantia nigra; 6-OHDA lesions; glutamate; behavioral recovery; striatal dopamine; microdialysis; NMDA antagonists; MK-801; CPP

This article has been cited by other articles:

				J. L. Tillerson, A. D. Cohen, J. Philhower, G. W. Miller, M. J. Zigmond, and T. Schallert Forced Limb-Use Effects on the Behavioral and Neurochemical Effects of 6-Hydroxydopamine J. Neurosci., June 15, 2001; 21(12): 4427 - 4435. [Abstract] [Full Text] [PDF]

				C. Flores, D. Rodaros, and J. Stewart Long-Lasting Induction of Astrocytic Basic Fibroblast Growth Factor by Repeated Injections of Amphetamine: Blockade by Concurrent Treatment with a Glutamate Antagonist J. Neurosci., November 15, 1998; 18(22): 9547 - 9555. [Abstract] [Full Text] [PDF]

				A. Emmi, H. Rajabi, and J. Stewart Behavioral and Neurochemical Recovery from Partial 6-Hydroxydopamine Lesions of the Substantia Nigra Is Blocked by Daily Treatment with D1/D5, But Not D2, Dopamine Receptor Antagonists J. Neurosci., May 15, 1997; 17(10): 3840 - 3846. [Abstract] [Full Text] [PDF]

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