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Effects of alpha-methyltyrosine on d-amphetamine-induced release of endogenously synthesized and exogenously administered catecholamines from the cat brain in vivo.

A cerebroventricular perfusing technique was utilized to measure the efflux of 3H-catecholamines from cat brain. After brain stores of catecholamines were labeled by an intraventricular injection of 3H-dopamine, the addition of d -amphetamine to the perfusing cerebrospinal fluid (CSF) increased the efflux of 3H-dopamine and 3H-norepinephrine; the presence of α-methyltyrosine (α-MT) in the CSF did not alter the amphetamine-induced response. Amphetamine also increased the efflux of 3H-catecholamines, which consisted almost entirely of 3H-dopamine after brain stores were labeled by an intraventricular infusion of 3H-tyrosine. The addition of α-MT to the CSF prior to and during the infusion of H3-tyrosine blocked the synthesis of 3H-catecholamines so that the subsequent administration of amphetamine failed to increase the efflux of these amines. However, if brain stores of catecholamines were first labeled by the infusion of 3H-tyrosine, the subsequent addition of α-MT to the CSF did not alter the amphetamine-induced efflux of 3H-catecholamines from the brain. Thus, the intraventricular infusion of α-MT blocks the synthesis of brain catecholamines, but it does not interfere with the ability of amphetamine to release these amines.