Backward walking induced by L-5-hydroxytryptophan in mice

An intraperitoneal administration of large doses of L-5-hydroxytryptophan (L-5HTP) induced dose-dependently a behaviour characterized by backward walking in mice. D-5-hydroxytryptophan (D-5HTP) and L-3,4-dihydroxyphenylalanine (L-DOPA) in the same doses failed to induce such behaviour. The backward walking induced by L-5HTP was blocked by a decarboxylase inhibitor, DL-alpha-methyl-DOPA, but was potentiated by a Monoamine Oxidase Inhibitor (MAOI), tranylcypromine or pargyline. An intracerebral injection of L-5-hydroxytryptamine (5-HT) induced a similar backward walking which was potentiated by a MAOI. The backward walking induced by L-5HTP was completely inhibited by 5-HT and dopamine (DA) receptor blockers, but was not inhibited by alpha- or beta-adrenergic blocker, antihistamine or anticholinergic drug. On the other hand, zimelidine and clomipramine, 5-HT uptake inhibitors, markedly potentiated the backward walking, while desipramine had no effect. From the results, it appears that excess amounts of 5-HT formed from L-5HTP produced the backward walking by directly stimulating the central 5-HT receptors, and DA is also involved in the behaviour. This behaviour may serve as a good model to assess the central serotonergic activity of drugs.