Duration-dependent increase in striatal glutamate following prolonged fluphenazine administration in rats.
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.
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Department of Psychology, Washington State University, Pullman 99164-4820, USA. sce@mail.wsu.edu
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D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005476:Fluphenazine / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D014150:Antipsychotic Agents; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005476:Fluphenazine