Changes in striatal electroencephalography and neurochemistry induced by kainic acid seizures are modified by dopamine receptor antagonists

James A. Bourne, Paul Fosbraey, John Halliday

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11 Citations (Scopus)

Abstract

We investigated the involvement of striatal dopamine release in electrographic and motor seizure activity evoked by kainic acid in the guinea pig. The involvement of the dopamine receptor subtypes was studied by systemic administration of the dopamine D1 receptor antagonist, R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH 23390; 0.5 mg kg-1), or the dopamine D2 antagonist, (5-aminosulphonyl)-N-[(1-ethyl-2-pyrrolidinyl)-methyl]-2-methoxybenzamide (sulpiride, 30 mg kg-1). Microdialysis and high performance liquid chromatography were used to monitor changes in extracellular levels of striatal dopamine and its metabolites, glutamate, aspartate and γ-amino-butyric acid (GABA). These data were correlated with changes in the striatal and cortical electroencephalographs and clinical signs. We found that, although neither dopamine receptor antagonist inhibited behavioural seizure activity, blockade of the dopamine D1-like receptor with SCH 23390 significantly reduced both the 'power' of the electrical seizure activity and the associated change in extracellular striatal concentration of glutamate, whilst increasing the extracellular striatal concentration of GABA. In contrast, blockade of the dopamine D2-like receptor with sulpiride significantly increased the extracellular, striatal content of glutamate and the dopamine metabolites. These results confirm previous evidence in other models of chemically-evoked seizures that antagonism of the dopamine D1 receptor tends to reduce motor and electrographic seizure activity as well as excitatory amino-acid transmitter activity, while antagonism of the dopamine D2 receptor has relatively less apparent effect.

Original languageEnglish
Pages (from-to)189-198
Number of pages10
JournalEuropean Journal of Pharmacology
Volume413
Issue number2-3
DOIs
Publication statusPublished - 16 Feb 2001

Keywords

  • (Guinea pig)
  • Dopamine receptor antagonist
  • Electroencephalography
  • in vivo
  • Kainic acid
  • Microdialysis
  • Seizure

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