Dizocilpine maleate, MK-801, but not 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline, NBQX, prevents transneuronal degeneration of nigral neurons after neurotoxic striatal–pallidal lesion

• Published in: Neuroscience 1999-04, Vol.90 (1), p.79-85
• Main Authors: DeGiorgio, L.A, DeGiorgio, N, Volpe, B.T
• Format: Article
• Language: English
• Subjects: 2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline; Animals; Biological and medical sciences; Corpus Striatum - drug effects; Corpus Striatum - physiology; Development. Senescence. Regeneration. Transplantation; Dizocilpine Maleate - pharmacology; Dizocilpine Maleate - therapeutic use; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Excitatory Amino Acid Antagonists - pharmacology; Excitatory Amino Acid Antagonists - therapeutic use; excitotoxicity; Fundamental and applied biological sciences. Psychology; Globus Pallidus - drug effects; Globus Pallidus - physiology; glutamate receptor; Ibotenic Acid - toxicity; Male; MK-801; NBQX; Nerve Degeneration - drug therapy; Neurons - drug effects; Neurons - pathology; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Neurotoxins - toxicity; Putamen - drug effects; Quinoxalines - pharmacology; Quinoxalines - therapeutic use; Rats; Rats, Wistar; Receptors, AMPA - antagonists & inhibitors; Receptors, Glutamate - drug effects; Substantia Nigra - drug effects; Substantia Nigra - physiology; substantia nigra pars reticulata; transneuronal degeneration; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(98)00428-X

Unilateral neurotoxin lesion of rat caudate–putamen and globus pallidus resulted in delayed, transneuronal degeneration of GABAergic substantia nigra pars reticulata neurons. To explore whether the disinhibition of endogenous glutamate excitatory input played a role in the degeneration of substantia nigra pars reticulata neurons, animals with unilateral striatal–pallidal lesions received three daily intraperitoneal injections of either dizocilpine maleate (MK-801, 1 or 10 mg/kg), an N-methyl- d-aspartate glutamate receptor blocker, or 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX, 30 mg/kg), an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor blocker, that began 24 h after the striatal–pallidal neurotoxin lesion. Drug treatment affected neither the volume of the initial lesion nor the volume of striatal–pallidal glial fibrillary acidic protein immunoreactivity. Neuron number in the substantia nigra pars reticulata ipsilateral to the lesioned striatopallidum was reduced on average by 37% in untreated control rats, in low dose MK-801, and NBQX-treated rats ( P