Neuroleptics increase striatal catecholamine metabolites but not ascorbic acid in dialyzed perfusate

To determine the effects of dopamine receptor blockade upon oxidizable components of striatal extracellular fluid, high-performance liquid chromatography (HPLC) with electrochemical detection was used to assay levels of ascorbic acid, dihydroxyphenylacetic acid (DOPAC) homovanillic acid (HVA), and 5-hydroxyindole acetic acid (5-HIAA) in perfusates obtained from unanesthetized rats following i.p. administration of haloperiodol (1.0 mg/kg) or clozapine (20 mg/kg). Striatal push-pull perfusion was performed by passing artificial CSF between two pulled glass micropipets, encapsulated by a hollow, semipermeable cellulose fiber, thereby limiting recovery to compounds under mw 5000. Samples were directly injected into a C-18 column at half-hour intervals before and after neuroleptic administration. Haloperidol administration resulted in increases in extracellular DOPAC and HVA while failing to alter 5-HIAA or ascorbic acid levels. Similar results were found with clozapine, except for a more variable individual response to the drug; clozapine also produced a small increase in 5-HIAA levels. Animals given a saline injection did not show increases in any of these compounds. These data confirm the involvement of extracellular dopamine metabolites in the electrochemical signal increases observed in vivo following dopamine receptor blockade and provide evidence that extracellular ascorbic acid in the striatum is insensitive to peripheral neuroleptic administration.