Time and dose influences on the behavioral effects of L-DOPA and 5-hydroxytryptophan after inhibition of extracerebral decarboxylase.

The influence of time and dose factors on the locomotor activity and gross behavioral effects of l-3,4-dihydroxyphenylalanine (L-DOPA) and 5-hydroxytryptophan (5-HTP) were assessed a albino mice pretreated with the peripheral decarboxylase inhibitor, MK-486, L-DOPA caused stereotyped behaviors and a decrease in orienting responses and locomotor activity, followed at the highest dose by increased locomotor activity. 5-HTP caused a dose-dependent increase in orienting responses and locomotor activity followed after 90 min by a dose-dependent decrease in locomotor activity. Administration of MK-486 and L-DOPA followed in the same animal by 5-HTP resulted in a diminution of the effects seen after either drug alone. This apparent antagonism may result from competition between the two amino acids at sites of membrane transport in the brain.