DETECTION OF CATECHOLAMINES IN BRAIN-TISSUE - SURFACE-MODIFIED ELECTRODES ENABLING INVIVO INVESTIGATIONS OF DOPAMINE FUNCTION

Recent evidence has shown that graphite paste electrodes modified with stearic acid show high resolution for catecholamines, dopamine (DA), and norepinephrine (NE), when implanted into brain tissue. The extent of this resolution has now been examined in more detail both in vitro and in vivo. Voltammetry at the modified electrodes at physiological pH shows DA and NE can be resolved from their major metabolites and precursors: 5-hydroxytryptamine and its principal metabolite and precursors, ascorbic acid and uric acid. Measurements with electrodes chronically implanted in conscious, unrestrained rats give voltammograms for DA in brain regions rich in DA nerve terminals with a peak potential similar to that observed for DA in vitro. This voltammogram is completely eliminated by selective lesions of DA neurons by 6-hydroxydopamine, is abolished by -butyrolactone (GBL), and is reduced to undetectable levels by the directly acting DA agonist apomorphine (APO). Combined, these findings demonstrate that the voltammograms represent DA efflux that originates from intact DA nerve terminals, depends on axonal conduction of nerve impulses (GBL), and is regulated by DA receptors controlling normal DA cell activity (APO). The electrodes exhibit reproducible, long-term stability in brain tissue, enabling continuous monitoring of DA efflux for periods of 2 months or more in individual animals. An example is provided demonstrating that chronic treatment with classical antipsychotic drugs decreases the basal efflux of DA in the striatum and nucleus accumbens, whereas “atypical” antipsychotic drugs decrease basal DA efflux only in the accumbens. Evidence is presented that the decreases, when observed, are due to the induction of depolarization block in DA neurons. These findings suggest that the inability of atypical antipsychotic drugs to decrease striatal DA efflux may be related to their low incidence of neurological side effects and that a decrease in limbic DA efflux may be involved in the delayed onset of therapeutic efficacy in man. © 1990, American Chemical Society. All rights reserved.