Disappearance of newly synthesized and total dopamine from the striatum of the rat after inhibition of synthesis: evidence for a homogeneous kinetic compartment.

Abstract

Abstract— The hypothesis that the biphasic disappearance of dopamine (DA) from the rat striatum following inhibition of synthesis with α‐methyl‐p‐tyrosine (AMPT) represents catabolism from separate‘functional’and 'storage’compartments (Javoy & Glowinski, 1971) was tested by administering 3H‐tyrosine i.v. 10 min before 400 mg per kg AMPT. The levels of newly synthesized 3H‐DA and total DA were then determined at 5‐min intervals. While both declined biphasically, the rate of decay of 3H‐DA was significantly less than that predicted by the two‐pool hypothesis. In fact, the patterns of change of 3H‐DA and total DA were identical and the specific activity of DA did not vary following AMPT. To determine if an increase in DA synthesis and release would result in the preferential catabolism of newly synthesized 3H‐DA, the experiment was repeated fol!owing treatment with 0.1 mg per kg haloperidol i.v. 3H‐DA and total DA still exhibited identical biphasic declines and there was no change in the specific activity of DA after AMPT even though 3H‐DA levels were increased three‐fold by haloperidol. Thus (a) no evidence for the preferential catabolism of newly synthesized 3H‐DA was obtained and (b) newly synthesized and total striatal DA behaved as if localized in a homogeneous kinetic compartment under all conditions employed.Rates of striatal DA metabolism were estimated in both experiments from changes in total DA after AMPT and by the formation of 3H‐DA in the initial 10 min after 3H‐tyrosine injection. Results of both approaches were consistent and indicated that the rates of striatal DA synthesis and catabolism may vary rapidly between approx. 20 and 90 nmol per g per h without violating single compartment kinetics. It is proposed that any labile pool contains no more than a few per cent of the DA in the striatum and the implications of this hypothesis are discussed.