Agents which reduce brain catechotamine concentrations by a release mechanism, for example reserpine, tetrabenazine and D,L-a-methyl-mtyrosine (a-M-m-T), increase motor activity in animals pretreated with a monoamine oxidase (MAO) inhibitor. According to many theorists, the released endogenous catecholamines, protected from intracellular oxidative deamination, exert a prolonged stimulant effect by means of their continued abundance at central adrcnergic receptors.
Depletion of brain catecholamines does not necessarily signify the operation of a release mechanism, however, and in fact there is good evidence to show that several recently discovered compounds probably deplete catecholamines by inhibiting biosynthesis at the rate-limiting tyrosine -+ dihydroxyphenylalanine (dopa) step (S~EcTO~ et al., 1965; UDE~FRIEND et al., 1965). Among the most potent tyrosine hydroxylase inhibitors thus far identified are the synthetic amino acids L-a-methyltyrosine (a-MT) (SP~cTo~ et al., 1965) and its m-iodinated derivative (UDE~F~IE~D et al., 1965; WEISSMA~ et al., 1966).
If tyrosine hydroxylase inhibitors such as a-MT do indeed reduce catecholamine concentrations in brain by inhibiting biosynthesis, and not by releasing catecholamines from storage sites, then they should not induce hyperactivity in the MAO-inhibited animal, since an abundance of free eatecholamines should not be available at central adrenergie receptors. The present motor activity studies in mice were undertaken to reinforce earlier observations (W~ISSMA~ and KoE, 1965), which showed that a-MT, unlike a-M-m-T, does not elicit gross stimulation in rats pretreated with MAO inhibitors.
Mice were Charles River males, Swiss CD strain, weighing approximately 20 g.