. However, it is not known whether the VP is necessary for salt appetite in terms of seeking out salt or consuming salt following sodium depletion. Here, we used a conditioned place-preference procedure to investigate the effects of optogenetically inhibiting the VP on context-driven salt seeking and the consumption of salt following deprivation. Male rats learned to associate one context with sucrose and another context with lessdesirable salt. Following sodium depletion, and in the absence of either sucrose or salt, we found that inhibiting the VP selectively reduced the elevation in time spent in the salt-paired context. VP inhibition had minimal effects on the consumption of salt once it was made available. To our knowledge, this is the first evidence that the VP or any brain region is necessary for the ability to use contextual cues to guide salt seeking. These results highlight a dissociation between deficit-driven reward seeking and reward consumption to replenish those deficits, with the former process being particularly sensitive to on-line VP activity.

We have previously demonstrated that voluntary exercise facilitates discrimination learning in a modified T-maze. There is evidence implicating the dorsolateral striatum (DLS) as the substrate for this task. The present experiments examined whether changes in DLS dopamine receptors might underlie the exercise-associated facilitation. Infusing a D1R antagonist into the DLS prior to discrimination learning facilitated the performance of nonexercising rats but not exercising rats. Infusing a D2R antagonist impaired the performance of exercising rats but not nonexercising rats. Exercise-associated facilitation of this task may rely on an exercise-induced decrease in D1R and increase in D2R activation in the DLS. Executive functions, such as working memory, cognitive flexibility , abstract thinking, and planning (Lezak 1982), are often the targets of research looking at the effects of exercise on human brain function. Meta-analysis of studies engaging older participants (ages 60-85) in exercise intervention programs suggests that exercise can improve several measures of cognition, but that the largest effects are on executive function (Hillman et al. 2008). Set-shifting is a measure of discrimination and cognitive flexibility used in both humans and rodents. Our lab has demonstrated that rats require fewer trials to reach the learning criterion of the initial discrimination phase of a set-shift task following 2 wk of voluntary wheel running (Eddy et al. 2013). In rodents, the initial discrimination in a set-shift task involves the dorsolateral striatum (DLS) (Palencia and Ragozzino 2005). This suggests that exercise is affecting the DLS in some way. One likely candidate is the dopamine (DA) system. There is abundant evidence that exercise impacts the striatal DA system (Gilliam et al. 1984; MacRae et al. 1987; Fisher et al. 2004; Pet-zinger et al. 2007; Foley and Fleshner 2008; Gerecke et al. 2010; Vuckovic et al. 2010), but these effects have not been linked to effects on learning. Therefore, the purpose of the current experiments was to test the hypothesis that changes in DLS DA receptors are responsible for our previously observed exercise-associated improvement in DLS-dependent discrimination learning (Eddy et al. 2013). D1 receptors (D1Rs) and D2 receptors (D2Rs) were the focus of these studies, as they are the most highly expressed DA receptors in the striatum (Valjent et al. 2009). As a starting place for this line of research, we used receptor antagonists to block the effects of striatal DA release during our task, with the reasoning that exercising and nonexercising rats would be affected differently. Male Wistar rats (n ¼ 9-13/group) obtained from Harlan Laboratories were used. Rats were between 59-and 63-d old when they arrived in the colony, and were housed individually. Rats assigned to the exercise group were given unlocked running wheels following colony acclimation. Nonexercise animals were given identical wheels that were locked in place to control for environmental enrichment effects. Rats had 24-h ...

Despite decades of research, investigations into effective neural and pharmacological therapies for many drugs of abuse, such as cocaine, have produced no FDA-approved approaches. This difficulty derives from the complexity of substance use disorders, which encompass a variety of behavioral, psychological, and neural circuit-based changes that occur as a result of repeated experience with the drug. Dopamine signaling has been demonstrated to play a key role in several aspects of drug abuse-from mediating its reinforcing properties and drug-seeking to triggering relapse-while also mediating a number of important aspects of normal (nondrug related) motivated behaviors and actions. Real-time recording methods such as in vivo voltammetry, electrophysiology, and calcium imaging demonstrate that the signaling properties of dopamine for motivationally relevant stimuli are highly dynamic and spatiotemporally circumscribed within afferent target regions. In this review, we identify the origins and functional consequences of heterogeneous dopamine release in the limbic system, and how these properties are persistently altered in the drug-experienced brain. We propose that these spatiotemporally parallel dopaminergic signals are simultaneously available to the animal, but that these circuits are impaired following prolonged drug experience by disrupting the location and content of dopamine signals in afferent target regions. These findings are discussed in the context of relapse and pathways to discovering new treatments for addiction disorders.