Functional increase in striatal dopaminergic activity following continuous long-term treatment with trifluoperazine

Acute administration of trifluoperazine (2-10 mg/kg i.p.) caused a dose-dependent increase in potassium (K+)-evoked release of [3H]acetylcholine from striatal slices, but was without effect on K+-evoked release of [3H]glutamate. K+-evoked [3H]acetylcholine release was not different in striatal tissue from rats receiving 1 year's continuous administration of trifluoperazine (4.5-5.1 mg/kg/day) compared to age-matched control animals. However, K+-evoked striatal [3H]glutamate release was decreased in tissue from chronically trifluoperazine-treated animals compared to age-matched controls. The reversal of the acute action of trifluoperazine on striatal [3H]acetylcholine and the decrease of [3H]glutamate release on chronic administration is consistent with adaptive changes in striatal dopamine transmission during long-term neuroleptic treatment.