Tyrosine augments acute clozapine- but not haloperidol-induced dopamine release in the medial prefrontal cortex of the rat: An in vivo microdialysis study

Tyrosine availability can influence dopamine (DA) synthesis in highly elect rophysiologically active DAergic neurons, such as those innervating the med ial prefrontal cortex (MPFC). Whether tyrosine concentrations can also affe ct MPFC extracellular DA concentrations, measured in vivo, is not known. Si nce clozapine preferentially activates mesocortical DA neurons, toe posited that tyrosine administration to a clozapine-pretreated vat would enhance t he clozapine-induced augmentation of MPFC extracellular DA concentrations. Tyrosine alone (25-50mg/kg IP) did not affect mesocortical or striatal extr acellular DA concentrations measured by in vivo microdialysis. Given 30 min utes after clozapine (10 mg/kg), tyrosine (50 mg/kg) significantly prolonge d the clozapine-induced increase in MPFC extracellular DA concentrations bu t had no effect in the striatum. In contrast, tyrosine (50 mg/kg) significa ntly prolonged the haloperidol (1 mg/kg) induced increase in striatal exrta cellular DA concentrations but had no effect in the MPFC. These data consti tute the first in vivo evidence that administration of tyrosine can selecti vely potentiate the clozapine-evoked increase in mesocortical extracellular DA concentrations. [Neuropsychopharmacology 25:149-156, 2001] (C) 2001 Ame rican College of Neuropsychopharmacology. Published by Elsevier Science Inc .