Intrastriatal methylmalonic acid administration induces rotational behavior and convulsions through glutamatergic mechanisms.
The effect of intrastriatal administration of methylmalonic acid (MMA), a metabolite that accumulates in methylmalonic aciduria, on behavior of adult male Wistar rats was investigated. After cannula placing, rats received unilateral intrastriatal injections of MMA (buffered to pH 7.4 with NaOH) or NaCl. MMA induced rotational behavior toward the contralateral side of injection and clonic convulsions in a dose-dependent manner. Rotational behavior and convulsions were prevented by intrastriatal preadministration of MK-801 and attenuated by preadministration of succinate. This study provides evidence for a participation of NMDA receptors in the MMA-induced behavioral alterations, where succinate dehydrogenase inhibition seems to have a pivotal role.
de Mello
C F
CF
Departamento de Química, Universidade Federal de Santa Maria, Brazil. cfmello@super.ufsm.br
Begnini
J
J
Jiménez-Bernal
R E
RE
Rubin
M A
MA
de Bastiani
J
J
da Costa
E
E
Wajner
M
M
D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology*; D007202:Indicators and Reagents; D008297:Male; D008764:Methylmalonic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D008845:Microinjections; D017072:Neostriatum / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012399:Rotation; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology; D013239:Stereotyped Behavior / Q000187:drug effects*; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors
D018691:Excitatory Amino Acid Antagonists; D007202:Indicators and Reagents; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D008764:Methylmalonic Acid; D013385:Succinate Dehydrogenase