Dopamine (DA) release varies within subregions and local environments of the striatum, suggesting that controls intrinsic and extrinsic to the DA fibers and terminals regulate release. While applying fast-scan cyclic voltammetry and using tonic and phasic stimulus trains, we investigated the regulation of DA release in the dorsolateral to ventral striatum. The ratio of phasic-to-tonic-evoked DA signals varied with the average ongoing firing frequency, and the ratio was generally higher in the nucleus accumbens (NAc) compared with the dorsolateral striatum. At the normal average firing frequency, burst stimulation produces a larger increase in the DA response in the NAc than the dorsolateral striatum. This finding was comparable whether the DA measurements were made using in vitro brain slices or were recorded in vivo from freely moving rodents. Blockade of the dopamine transporters and dopamine D 2 receptors particularly enhanced the tonic DA signals. Conversely, blockade of nicotinic acetylcholine receptors (nAChRs) containing the  2 subunit ( 2 *) predominantly suppressed tonic DA signals. The suppression of tonic DA release increased the contrast between phasic and tonic DA signals, and that made the frequencydependent DA dynamics between the dorsolateral striatum and NAc more similar. The results indicate that intrinsic differences in the DA fibers that innervate specific regions of the striatum combine with (at least) DA transporters, DA receptors, and nAChRs to regulate the frequency dependence of DA release. A combination of mechanisms provides specific local control of DA release that underlies pathway-specific information associated with motor and reward-related functions. Dopamine (DA) neurons operate in distinct tonic and phasic timescales to differentiate behaviorally relevant information (Schultz, 2007). DA neurons discharge tonically at low frequencies that consist of individual action potentials without bursts . Periodically, DA neurons fire in phasic bursts of near 20 Hz and greater (Hyland et al., 2002;Robinson et al., 2004). Evidence indicates that phasic or burst firing induces greater extracellular DA release compared with tonic, single-spike firing activity (Gonon, 1988;Grace, 1991;Floresco et al., 2003). Those tonic and phasic signals arise from midbrain DA neurons of the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) that innervate the whole dorsal to ventral extent of the striatum. Although the DA neurons that project to the prefrontal cortex may have higher discharge rates (Chiodo et al., 1984;Lammel et al., 2008), many midbrain DA neurons often exhibit similar overall firing properties (Schultz, 1986;Clark and Chiodo, 1988;Gariano et al., 1989;Robinson et al., 2004). Reward-related sensory input, however, such as that initiated by an addictive drug, enhances DA release to varying degrees depending on the dopaminergic pathway and target region (Pontieri et al., 1996;Nisell et al., 1997;Shi et al., 2000;Di Chiara et al., 2004;Janhunen and Ahtee, 2007). Th...