Acute neuroleptic stimulates DOPA decarboxylase in porcine brain in vivo

The activity of DOPA decarboxylase measured in homogenates from rat striatu m, or calculated from the rate of tracer decarboxylation measured ex vivo, is stimulated following acute treatment with antagonists of dopamine D2-lik e receptors. We used compartmental kinetics to test the hypothesis that uti lization of the DOPA decarboxylase substrate [F-18]fluorodopa is potentiate d in living striatum following acute treatment with a typical neuroleptic. The kinetics of the tracer uptake were determined in eight anesthetized fem ale pigs (40 kg) and in three animals receiving an infusion of haloperidol (75 mug kg(-1) h(-1)) for 1 h prior to tracer administration and throughout the 2-h positron emission recording. The relative activity of DOPA decarbo xylase in striatum was increased threefold by the treatment. This potentiat ion of DOPA decarboxylation after pharmacological blockade of dopamine D2-l ike receptors may be used to optimize the utilization of exogenous DOPA in the treatment of Parkinson's disease. (C) 2001 Wiley-Liss, Inc.