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.