ABSTRACT
Drugs such as p-chloroamphetamine or a combination of tranylcypromine and tryptophan release serotonin in the central nervous system and produce a behavioral serotonin syndrome. However, in the presence of methysergide or following destruction of descending spinal serotonergic projections by 5,7-dihydroxytryptamine, central serotonin release produces hyperlocomotion. This supports the hypothesis that release of serotonin in the brain promotes locomotion but that the expression of this effect can be blocked by concomitant intraspinal effects of serotonin release. Hyperlocomotion induced by serotonin release is attenuated or blocked by: (a) pretreatment with p-chlorophenylalanine; (b) acute surgical lesions of the basal diencephalon; (c) chronic lesions of the ventromedial midbrain tegmentum by local injection of 5,7-dihydroxytryptamine; and (d) acute surgical decortication. Medial decortication tends to be more effective then lateral decortication. Hyperlocomotion produced by methamphetamine is also attenuated or blocked by acute basal diencephalic lesions or decortication. It is suggested that ascending serotonergic and dopaminergic projections collaborate in the generation of spontaneous voluntary motor activity.