SPECIFIC INHIBITION BY -METHYLTYROSINE OF AMPHETAMINE-INDUCED AMINE RELEASE FROM BRAIN

¹ Department of Pharmacology, University of Texas Southwestern Medical School, Dallas, Texas

It has been reported that l--methyltyrosine (l--MT) in the rat, at a time of little overt sedation or amine depletion, blocks amphetamine-induced central effects, but not those induced by methylphenidate. It has been suggested that amphetamine acts centrally solely through release of newly synthesized catecholamine. To examine other possible actions of l-MT, rat brain slices were incubated with tritium-labeled metaraminol or norepinephrine. Subsequeint exposures to d-amphetamine (10^-5 M) evoked release of tritium. The presence of l--MT (5 x 10^-6 M) did not affect metaraminol release by initial exposure to amphetamine, but markedly inhibited the response to a second exposure. d--MT did not show this effect. In norepinephrine-loaded slices, l--MT inhibited norepinephrine release by both the initial and second amphetamine exposure. Amine release by methylphenidate (10^-4 M) or by electrical field stimulation was not affected by l--MT. Experiments in vivo showed that the lowering of hypothalamic metaraminol in the rat following amphetamine injection was inhibited by prior administration of l--MT. The results suggest that l--MT may not only inhibit tyrosine hydroxylase activity, but may prevent amphetamine central actions by inhibition of brain amine release, possibly by blocking amine transfer from a general store to an amphetamine-releasable site.