Tyrosine hydroxylase inhibition by cycloheximide and anisomycin is not responsible for their amnesic effect.

It has been reported that the administration of cycloheximide, a protein synthesis inhibitor, depresses brain tyrosine hydroxylase activity as measured in vitro. This finding raised the possibility that the amnesic effect of this drug could be due to reduction of norepinephrine synthesis rather than to inhibition of protein synthesis required for long-term memory. We have found that (1) amnesic doses of cycloheximide and anisomycin, two protein synthesis inhibitors, produced measurable depression of tyrosine hydroxylase activity although much of the depression may be due to isotope dilution rather than true inhibition, and (2) a-methyl-p-tyrosine a competitive inhibitor of tyrosine hydroxylase, in doses which depressed tyrosine hydroxylase activity as much as or more than either cycloheximide or anisomycin, did not affect memory. Therefore the effect of protein synthesis inhibitors on brain tyrosine hydroxylase activity is not sufficient to explain their amnesic effect.