A comparison of the effects of acute and one year's continuous neuroleptic treatment on the release of [3H]glutamate and [3H]acetylcholine from rat striatal slices.

ABSTRACT

The effect of neuroleptic drugs administered acutely or continuously for 1 year on the release of [3H]glutamate and [3H]acetylcholine from striatal slices in vitro has been compared. Acute in vivo administration of haloperidol, trifluoperazine and clozapine increased the potassium-evoked release of [3H]acetylcholine from striatal slices in a dose-dependent fashion, whereas sulpiride was without effect. None of the neuroleptics given acutely had any effect on the potassium-evoked striatal release of [3H]glutamate. Potassium-evoked striatal release of [3H]acetylcholine in animals receiving 1 year's continuous administration of haloperidol, trifluoperazine or sulpiride was no different from that in age-matched control animals, but was less than controls in animals receiving clozapine for 1 year. All drugs caused a decrease in potassium-evoked striatal [3H]glutamate release following drug administration for 1 year compared to age-matched controls. The reversal of the acute action of neuroleptic drugs on striatal [3H]acetylcholine and [3H]glutamate release is consistent with a functional increase in striatal dopamine transmission following long-term neuroleptic treatment.