Rat brain concentration of administered amino acids: dependence on time of day for administration.

Several large neutral amino acids (LNAA) (e.g. L-DOPA and L-tryptophan) are used as therapeutic agents. To reach the brain they have to compete with the naturally occurring large neutral amino acids for the saturable, carrier mediated transport into the brain. Since the concentration of LNAA in plasma demonstrates a diurnal rhythm, this competition could be expected to vary accordingly. To investigate if this variation could influence the brain concentration of a certain administered amino acid we injected three groups of rats with L-DOPA, L-tryptophan or saline in the afternoon when the rat plasma concentration of LNAA is at its lowest. Three other groups of rats received the same treatments at 3 a.m., when the concentration of LNAA is reported to be at a maximal level. The brain concentrations of the administered amino acids were significantly higher and LNAA in plasma lower in the groups injected in the afternoon compared with those injected during the night. These findings support the hypothesis that the time of the day when an amino acid is administered is of importance to the concentration of the administered amino acid in the brain.