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.