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 (A LA) (1-8 mu mol/2 mu l), a metabolite that accumulates in porphyrias, was e valuated. ALA administration to adult female rats increased locomotor activ ity, induced clonic convulsions and elicited dose-dependent body asymmetry assessed by the elevated body swing test. ALA-induced convulsions were prev ented by intrastriatal preadministration of the glutamate antagonists, 6,7- dinitroquinoxaline-2,3-dione (8 nmol/0.5 mu l) or dizocilpine (2.5 nmol/0.5 mu l), but not by the GABA agonist, muscimol (46 pmol/0.5 mu l). Body asym metry was prevented only by 6,7-dinitroquinoxaline-2,3-dione pretreatment. A higher dose of muscimol (92 pmol/0.5 mu l) prevented both ALA-induced con vulsions and body asymmetry. However, this dose of muscimol induced motor b iases, which make difficult to ascertain the involvement of GABA(A) recepto rs in ALA-induced behavioral effects. This study suggests that glutamatergi c mechanisms underlie the ALA-induced convulsions and body asymmetry. The p resent results may be of value in understanding the physiopathology of the neurological dysfunction occurring in acute porphyrias. (C) 2000 Elsevier S cience B.V. All rights reserved.