, 2007, 2012). Considerable evidence indicates that mesolimbic DA is part of a broader circuitry regulating behavioral activation and effort-related functions, which includes other transmitters (adenosine,

GABA; Mingote et al., 2008; Farrar et al., 2008, 2010; Nunes et al., 2010; Salamone et al., 2012) and brain areas (basolateral amygdala, anterior Torin 1 datasheet cingulate cortex, ventral pallidum; Walton et al., 2003; Floresco and Ghods-Sharifi, 2007; Mingote et al., 2008; Farrar et al., 2008; Hauber and Sommer, 2009). Although it is sometimes said that nucleus accumbens DA release or the activity of ventral tegmental DA neurons is instigated by presentation of positive reinforcers such as food, the literature describing the response of mesolimbic DA to appetitive stimuli is actually quite complicated OTX015 supplier (Hauber, 2010). In a general sense, does food presentation increase DA neuron activity or accumbens DA release? Across a broad range of conditions, and through different phases of motivated behavior, which phases or

aspects of motivation are closely linked to the instigation of dopaminergic activity? The answer to these questions depends upon the timescale of measurement, and the specific behavioral conditions being studied. Fluctuations in DA activity can take place over multiple timescales, and a distinction often is made between “phasic” and “tonic” activity (Grace, 2000; Floresco et al., 2003; Goto and Grace, 2005). Electrophysiological recording techniques are capable of measuring fast phasic activity of putative DA neurons (e.g., Schultz, 2010), and voltammetry methods (e.g., fast cyclic voltammetry) record DA “transients” that are fast

phasic changes in extracellular DA, which are thought to represent the release from bursts of DA neuron activity (e.g., Roitman et al., 2004; Sombers et al., 2009; Brown et al., 2011). It also has been suggested that fast phasic changes in DA release can be relatively independent Calpain of DA neuron firing, and can instead reflect synchronized firing of cholinergic striatal interneurons that promote DA release through a presynaptic nicotinic receptor mechanism (Rice et al., 2011; Threlfell et al., 2012; Surmeier and Graybiel, 2012). Microdialysis methods, on the other hand, measure extracellular DA in a way that represents the net effect of release and uptake mechanisms integrated over larger units of time and space relative to electrophysiology or voltammetry (e.g., Hauber, 2010). Thus, it is often suggested that microdialysis methods measure “tonic” DA levels.