Hippocampal and cerebellar extracellular amino acids during pilocarpine-induced seizures in freely moving rats

Eur J Pharmacol. 1997 Jan 14;319(1):21-9. doi: 10.1016/s0014-2999(96)00830-8.

Abstract

Limbic seizures were provoked in freely moving rats by intrahippocampal administration of the muscarinic receptor agonist pilocarpine via a microdialysis probe (10 mM for 40 min at 2 microliters/min). Changes in extracellular hippocampal and cerebellar glutamate, aspartate and gamma-aminobutyric acid (GABA) levels were monitored during and after pilocarpine administration. Effects of systemic or local administration of anticonvulsants on the seizures and concomitant changes in amino-acid concentrations, were investigated. Pilocarpine-induced seizures were completely abolished after intraperitoneal premedication for 7 days with phenobarbital (15 mg/kg per day) and after intrahippocampal administration of 10 mM phenobarbital and 1 mM carbamazepine (180 min at 2 microliters/min). Rats premedicated with carbamazepine (5 mg/kg per day) still developed seizures. The changes in extracellular hippocampal amino-acid levels suggest that glutamate, aspartate and GABA are not involved in seizure onset, but may play a role in seizure maintenance and/or spread in the pilocarpine animal model of epilepsy. The increases in extracellular amino acids in ipsi- and contralateral cerebellum following limbic seizures provoked in the hippocampus, probably play a role in the 'reversed' diaschisis phenomenon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / analysis*
  • Animals
  • Aspartic Acid / analysis
  • Carbamazepine / pharmacology
  • Cerebellum / chemistry*
  • Glutamic Acid / analysis
  • Hippocampus / chemistry*
  • Male
  • Microdialysis
  • Phenobarbital / pharmacology
  • Pilocarpine / pharmacology*
  • Rats
  • Rats, Wistar
  • Seizures / chemically induced
  • Seizures / metabolism*
  • gamma-Aminobutyric Acid / analysis

Substances

  • Amino Acids
  • Pilocarpine
  • Aspartic Acid
  • Carbamazepine
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Phenobarbital