The effects of Cycloheximide and Anisomycin on monoamine synthesis in a brain synaptosome preparation

Cycloheximide (100 mg/kg) and anisomycin (50 mg/kg) decreased the synthesis of [3H]-dopamine (DA) and [3H]-5-hydroxytryptamine (5-TH) from their labelled amino acid precursors in a brain synaptosomal preparation on hour after drug administration in vivo. Treatment with anisomycin also decreased synthesis of [3H]-norepinephrine (NE). Anisomycin (1mM) decreased the accumulation of newly snythesized monoamines when added to the synaptosomal preparation in vitro, while cycloheximide (1mM) impaired only [3H]-norepinephrine formation. All drug-induced decreases in the accumulation of newly synthesized 5-hydroxytryptamine were associated with concomitant decreases in the accumulation of [3H]-tryptophan (Trp) by the synaptosome fraction, suggesting that the drugs may act in part by decreasing precursor availability. However, the same correlation was not observed between [3H]-catecholamine synthesis and [3H]-tyrosine (try) content of the synaptosomal fraction. Comparison of the results obtained after in vivo and in vitro administration of these drugs indicates that cycloheximide may exert many of its effects on monoamine synthesis via a metabolite, while anisomycin appears to act directly.