Central and peripheral effects of 5-hydroxytryptophan on motor activity in mice.

Abstract

Spontaneous motor activity was studied in mice given dl-5-hydroxytryptophan (5-HTP) i.p. in doses ranging from 6.25 to 800 mg/kg with and without previous administration of l-α-hydrazino-α-methyl-β-(3,4-dihydroxyphenyl)-propionic acid (MK-486), an inhibitor of peripheral amino acid decarboxylase. Some mice were also given repeated injections of dl-α-methyl-metatyrosine (α-MMT) prior to MK-486 and 5-HTP. The brain levels of noradrenaline (NA), dopamine (DA) and 5-hydroxytryptamine (5-HT) were also determined in these animals. 5-HTP in doses between 100 and 800 mg/kg caused a decrease in motor activity when given alone, whereas after pretreatment with MK-486 it increased motor activity. Lower doses of 5-HTP, alone or in combination with MK-486, had no significant effect on motor activity. Pretreatment with α-MMT caused a marked depletion of NA and DA without counteracting the increase in motor activity induced by MK-486 and 5-HTP. It is concluded that the central effects of large doses of 5-HTP are excitatory whilst the effects outside the blood-brain barrier have an inhibitory influence on the motor activity in mice. The mechanisms for the central excitatory effects are discussed.