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 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.
Emmi
A
A
Department of Psychology, Concordia University, Montréal, Québec, Canada.
Rajabi
H
H
Stewart
J
J
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004334:Drug Administration Schedule; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology
D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D016291:Dizocilpine Maleate; D016627:Oxidopamine; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid