3-METHOXYTYRAMINE IS THE MAJOR METABOLITE OF RELEASED DOPAMINE IN THERAT FRONTAL-CORTEX - REASSESSMENT OF THE EFFECTS OF ANTIPSYCHOTICS ONTHE DYNAMICS OF DOPAMINE RELEASE AND METABOLISM IN THE FRONTAL-CORTEX, NUCLEUS-ACCUMBENS, AND STRIATUM BY A SIMPLE 2-POOL MODEL

3-Methoxytyramine (3-MT) and 3,4-dihydroxyphenylacetic acid (DOPAC) ra tes of formation were used, respectively, to assess the dynamics of do pamine (DA) release and turnover in the rat frontal cortex, nucleus ac cumbens, and striatum. Assuming total (re)uptake and metabolism of rel eased DA are relatively uniform among the three brain regions, a simpl ified two pool model was used to assess the metabolic fate of released DA. Under basal conditions, 3-MT formation was found to comprise >60% of total DA turnover (sum of 3-MT plus DOPAC rates of formation) in t he frontal cortex, and not more than 15% in the nucleus accumbens and striatum. Haloperidol increased the 3-MT rate of formation to a greate r extent in the frontal cortex than in the two other regions. Clozapin e increased the 3-MT rate of formation in the frontal cortex and decre ased it in the striatum. Both drugs increased DOPAC rate of formation in the frontal cortex and nucleus accumbens. It was elevated by halope ridol but not clozapine in the striatum. It is concluded that (1) O-me thylation is a prominent step in the catabolism of DA in the frontal c ortex under both physiological conditions and after acute treatment wi th antipsychotics, (2) 3-MT is the major metabolite of released DA in the frontal cortex and possibly also in the nucleus accumbens and stri atum, (3) in contrast to the frontal cortex, most of the DOPAC in the nucleus accumbens and striatum appear to originate from intraneuronal deamination of DA that has not been released, (4) because presynaptic uptake and metabolism of DA give rise to DOPAC, whereas postsynaptic u ptake and metabolism produced both DOPAC and 3-MT, the ratio of 3-MT t o DOPAC rates of formation can be a useful index of reuptake inhibitio n.