Effects of amino acid alterations caused by protein synthesis inhibitors on brain monoamine formation.

Cerebral amino acid concentrations in mice were determined following in vivo treatment with cycloheximide and anisomycin. Synaptosomes from untreated mice were then exposed to concentrations of amino acids designed to simulate the conditions existing extraneuronally following in vivo drug treatment. The synthesis of [3H]norepinephrine, [3H]dopamine and [3H]5-hydroxytryptamine from their labelled amino acid precursors was determined, as well as the accumulation of the precursors by the synaptosomes. Although the synthesis of both [3H]dopamine and [3H]norepinephrine was decreased below expected values predicted from samples in which only tyrosine was altered to represent the concentrations following drug treatment, it was not decreased significantly below control levels. Synthesis of [3H]5-hydroxytryptamine was increased in the presence of amino acid mixtures simulating drug treatment. The results suggest that alteration of amino acid levels is not involved in the inhibition of brain monoamine synthesis caused by these protein synthesis inhibitors.