Acute and subacute effects of neuroleptics dopamine synthesis and release in the rat striatum

The effects of acute and subacute treatments with moderate doses of thioproperazine and haloperidol on dopamine synthesis and release have been examined in rat striatal slices. Synthesis and release of dopamine were determined by measuring the rate of formation of 3H-H2O during the conversion of L3,5-3H-tyrosine into 3H-Dopa and the accumulation of newly synthesized 3H-dopamine in striatal slices and their incubating medium. Possible effects of the treatments on tyrosine striatal levels or tyrosine specific activity were also investigated. Dopamine synthesis rate was markedly accelerated 2.5 hrs after the acute injection of thioproperazine, but was equal to control levels 24 hrs later. The effects of thioproperazine and haloperidol were thus determined 2.5 and 24 hrs after an acute injection and following the last injection of a repeated daily treatment of 11 days. Dopamine synthesis and release were still markedly increased 2.5 hrs after the last injection of the subacute neuroleptic treatments when compared to controls, but these effects were less pronounced than those observed 2.5 hrs after an acute injection of either drug. Conversely, dopamine synthesis and release were significantly decreased 24 hrs after the last injection of the subacute neuroleptic treatments when compared to controls. Two hypotheses are proposed to explain the changes in dopamine synthesis induced by repeated treatments with neurolptics.