Duration-dependent increase in striatal glutamate following prolonged fluphenazine administration in rats

Eur J Pharmacol. 1996 Jul 25;308(3):279-82. doi: 10.1016/0014-2999(96)00333-0.

Abstract

Chronic neuroleptic administration has been shown to selectively increase striatal extracellular glutamate concentration. In the current study, age-matched female rats were administered chronic oral fluphenazime or no drug via their drinking water for 3 or 32 weeks. Microdialysis probes were inserted into the ventrolateral caudate putamen and the medial nucleus accumbens and dialysis samples were analyzed for glutamate and gamma-aminobutyric acid (GABA) concentrations Glutamate levels were significantly increased only in the ventrolateral caudate putamen after 32 weeks. No significant effects were seen for GABA levels. Neuroleptic-induced enhancement of striatal glutamate levels thus appears to increase with chronic exposure and this increase may relate to late onset motor side effects.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Chromatography, High Pressure Liquid
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Female
  • Fluphenazine / pharmacology*
  • Glutamic Acid / metabolism*
  • Microdialysis
  • Rats
  • Rats, Sprague-Dawley
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Antipsychotic Agents
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Fluphenazine