Spermine attenuates behavioral and biochemical alterations induced by quinolinic acid in the striatum of rats.
Polyamines are aliphatic amines containing nucleophilic centers that are found in all eukaryotic cells, including brain cells. These compounds determine neuroprotection in experimental models of cerebral ischemia and neurotoxicity. In the current study we investigated the protective effects of spermine, an agonist of the polyamine binding site at the N-methyl-d-aspartate receptor, against the behavioral and neurochemical alterations induced by quinolinic acid. The unilateral intrastriatal injection of quinolinic acid (180 nmol/site into the dorsal striatum) induced stereotypical motor asymmetries, assessed by the open field and elevated body swing tests. Spermine modulated quinolinic acid-induced rotational behavior biphasically. While the previous intrastriatal administration of spermine at the dose of 0.1 nmol/site increased, the administration of spermine at the dose of 10 nmol/site reduced quinolinic acid-induced rotational behavior. Spermine (10 nmol/site) also decreased the contralateral swing behavior induced by quinolinic acid. Furthermore, the effect of 10 nmol of spermine was counteracted by the co-administration of arcaine (10 nmol), a selective antagonist of the polyamine binding site at the N-methyl-d-aspartate receptor. In addition, spermine (10 nmol) protected against quinolinic acid-induced protein carbonylation in the rat striatum, further suggesting an antioxidant role for this polyamine. These results provide evidence that the behavioral and biochemical alterations induced by quinolinic acid are attenuated or prevented by spermine through its interaction with N-methyl-d-aspartate receptor and/or its antioxidant function.
Velloso
Nádia Aléssio
NA
Department of Chemistry, Center of Exact and Natural Sciences, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
Dalmolin
Gerusa Duarte
GD
Fonini
Graciela
G
Gindri Sinhorin
Valéria Dornelles
VD
Ferreira da Silveira
Aron
A
Rubin
Maribel Antonello
MA
Mello
Carlos Fernando
CF
D000818:Animals; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001645:Biguanides / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011805:Quinolinic Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D013096:Spermine / Q000378:metabolism* / Q000494:pharmacology
D000975:Antioxidants; D001645:Biguanides; D018691:Excitatory Amino Acid Antagonists; D011805:Quinolinic Acids; D016194:Receptors, N-Methyl-D-Aspartate; D013096:Spermine; C006624:arcaine