Intrastriatal administration of 5-aminolevulinic acid induces convulsions and body asymmetry through glutamatergic mechanisms

Brain Res. 2000 Jun 16;868(1):88-94. doi: 10.1016/s0006-8993(00)02327-1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminolevulinic Acid / pharmacology*
  • Animals
  • Convulsants / pharmacology*
  • Corpus Striatum / drug effects
  • Corpus Striatum / physiopathology*
  • Dizocilpine Maleate / pharmacology
  • Epilepsy / chemically induced*
  • Epilepsy / drug therapy
  • Excitatory Amino Acid Antagonists / pharmacology
  • Female
  • GABA Agonists / pharmacology
  • Glutamic Acid / physiology*
  • Microinjections
  • Muscimol / pharmacology
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Wistar
  • gamma-Aminobutyric Acid / physiology

Substances

  • Convulsants
  • Excitatory Amino Acid Antagonists
  • GABA Agonists
  • Quinoxalines
  • Muscimol
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • FG 9041
  • Dizocilpine Maleate
  • Aminolevulinic Acid