Chronic haloperidol treatment impairs glutamate transport in the rat striatum.
High-affinity, Na(+)-dependent transport of glutamate into neurons and glial cells maintains the extracellular concentration of this neurotransmitter at a sub-toxic level. Chronic blockade of dopamine D(2) receptors with haloperidol elevates extracellular glutamate levels in the striatum. The present study examines the effect of long-term haloperidol treatment on glutamate transporter activity using an assay based on measuring the uptake of D-[3H]aspartate in striatal synaptosomes prepared from male Wistar rats. The maximal rate of glutamate transport in the striatum is reduced by 63% following 27 weeks of haloperidol treatment. This impairment of glutamate transport may be important in chronic neuroleptic drug action.
De Souza
I E
IE
Department of Anatomy, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin, Ireland. idesouza@rcsi.ie
McBean
G J
GJ
Meredith
G E
GE
D000818:Animals; D001224:Aspartic Acid / Q000493:pharmacokinetics; D001692:Biological Transport / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000493:pharmacokinetics*; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014316:Tritium
D018492:Dopamine Antagonists; D014316:Tritium; D001224:Aspartic Acid; D018698:Glutamic Acid; D006220:Haloperidol