g., increases followed by decreases) in extracellular DA that take place over minutes, it is perhaps most useful to employ the term “fast phasic” to talk about the rapid changes in DA-related activity that can be measured with electrophysiology or voltammetery, and “slow phasic” in reference to the changes that take place over the slower time scale measured

with microdialysis methods (e.g., Hauber, 2010; Segovia et al., 2011). Electrophysiology studies have shown that presentation of novel or unexpected food reinforcers is accompanied by transient increases in the activity of putative ventral tegmental DA neurons, but that this effect goes away with regular presentation, or repeated exposure through training (Schultz et al., 1993; Schultz, 2010). Employing voltammetry Romidepsin methods to measure fast phasic changes in DA release, Roitman et al. (2004) showed that, in trained animals, exposure to a conditioned stimulus signaling that lever pressing would result in sucrose delivery was accompanied by an increase in DA transients, however, the actual

presentation of the sucrose reinforcer was not. A similar finding was reported years ago by Nishino et al. (1987), who studied free-operant fixed ratio lever pressing in monkeys and observed that activity of putative ventral tegmental DA neurons was increased during lever pressing in trained animals but actually decreased during reinforcer presentation. Unpredicted food delivery, as well as presentation of cues that predicted food delivery, increased fast phasic signaling as measured by voltammetry in Selleckchem VX809 the nucleus accumbens core (Brown et al., 2011). DiChiara and colleagues showed that exposure to novel palatable foods transiently

increased extracellular DA in nucleus accumbens shell as measured by microdialysis, but that this response rapidly habituated (e.g., Bassareo et al., 2002). A recent microdialysis paper demonstrated that presentation of high carbohydrate food reinforcers to previously exposed rats did not produce any change in extracellular DA in accumbens core or shell (Segovia et al., 2011). In contrast, both the acquisition and maintenance of fixed ratio lever pressing was associated with increases in DA release (Segovia et al., 2011). A similar pattern was shown when markers of DA-related signal transduction (c-Fos and DARPP-32) were very measured (Segovia et al., 2012). Taken together, these studies do not support the idea that food presentation per se, including that of palatable foods, uniformly increases accumbens DA release across a broad range of conditions. Nevertheless, considerable evidence does indicate that increases in DA transmission are associated with presentation of stimuli associated with natural reinforcers such as food, or the performance of instrumental behavior; this has been seen in studies involving microdialysis (Sokolowski and Salamone, 1998; Ostlund et al., 2011; Hauber, 2010; Segovia et al., 2011), voltammetry (Roitman et al., 2004; Brown et al.