Central dopamine systems are key players in the cerebral organization of behavior and in various neurological and psychiatric diseases. We demonstrate the presence of a neurochemical feed-forward loop characterized by region-specific changes in dopamine efflux in serially connected striatal regions, providing evidence in favor of the existence of so-called spiraling striato-nigro-striatal connections. Using in vivo microdialysis of rats, we show that simultaneous stimulation of dopamine D-1 and D-2 receptors in the accumbal shell decreased dorsal striatal dopamine efflux via a direct or indirect feed-forward loop involving shell, core, ventrolateral and dorsal part of the striatum: simultaneous stimulation of dopamine D-1 and D-2 receptors in the shell decreased dopamine efflux in the core; flupenthixol-induced inhibition of dopamine D-1 and D-2 receptors in the core increased dopamine efflux in the ventrolateral part of the striatum, and simultaneous stimulation of dopamine D-1 and D-2 receptors in the ventrolateral part of the striatum decreased dopamine efflux in the dorsal part of the striatum. Finally, simultaneous stimulation of dopamine D-1 and D-2 receptors in the shell decreased dopamine efflux in the dorsal part of the striatum. Thus, distinct striatal regions act also in series, providing a better understanding of the neural mechanisms underlying dopamine-dependent behaviors and the progression of dopamine-dependent disorders such as depression, schizophrenia, attention deficit hyperactivity disorder (ADHD), and addiction. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.