Destruction of dopamine terminals within the nucleus accumbens (N.Acc.) with 6-hydroxydopamine blocked the locomotor activating properties of d-amphetamine, but not caffeine or corticotropin-releasing factor (CRF). Infusion of muscimol into the region of nucleus accumbens efferent terminals in the substantia innominata and lateral preoptic region (SI/LPO) blocked amphetamine-, but not caffeine- or CRF-stimulated locomotion. These muscimol infusions also blocked heroin-stimulated locomotion. These results suggest that amphetamine, acting through a process dependent on N.Acc. dopamine transmission, stimulates locomotion by decreasing GABAergic activity within this N.Acc.-SI/LPO projection; heroin, known to act through a process dependent on N.Acc. opiate receptor activation, also stimulates locomotion by decreasing GABAergic activity within the SI/LPO; caffeine and CRF produce their activation through different neural substrates.