Intrastriatal administration of 5-aminolevulinic acid induces convulsions and body asymmetry through glutamatergic mechanisms.
The involvement of glutamatergic and GABAergic mechanisms in the behavioral effects induced by the intrastriatal injection of 5-aminolevulinic acid (ALA) (1-8 mgr;mol/2 mgr;l), a metabolite that accumulates in porphyrias, was evaluated. ALA administration to adult female rats increased locomotor activity, induced clonic convulsions and elicited dose-dependent body asymmetry assessed by the elevated body swing test. ALA-induced convulsions were prevented by intrastriatal preadministration of the glutamate antagonists, 6, 7-dinitroquinoxaline-2,3-dione (8 nmol/0.5 microl) or dizocilpine (2. 5 nmol/0.5 microl), but not by the GABA agonist, muscimol (46 pmol/0. 5 microl). Body asymmetry was prevented only by 6, 7-dinitroquinoxaline-2,3-dione pretreatment. A higher dose of muscimol (92 pmol/0.5 microl) prevented both ALA-induced convulsions and body asymmetry. However, this dose of muscimol induced motor biases, which make difficult to ascertain the involvement of GABA(A) receptors in ALA-induced behavioral effects. This study suggests that glutamatergic mechanisms underlie the ALA-induced convulsions and body asymmetry. The present results may be of value in understanding the physiopathology of the neurological dysfunction occurring in acute porphyrias.
Emanuelli
T
T
Departamento de Tecnologia e Ciência de Alimentos, Centro de Ciências Rurais, Universidade Federal de Santa Maria, Campus - Camobi, 97105-900, RS, Santa Maria, Brazil. tati@ccr.ufsm.br
Prauchner
C A
CA
Dacanal
J
J
Zeni
A
A
Reis
E C
EC
de Mello
C F
CF
de Souza
D O
DO
D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000818:Animals; D003292:Convulsants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004827:Epilepsy / Q000139:chemically induced* / Q000188:drug therapy; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology*; D008845:Microinjections; D009118:Muscimol / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D003292:Convulsants; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D011810:Quinoxalines; D009118:Muscimol; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C056723:FG 9041; D016291:Dizocilpine Maleate; D000622:Aminolevulinic Acid