Background

The salt appetite phenomenon was first discovered by Richter (1936), who found that rats began to immediately consume a 1% salt solution in greater quantities compared to water in a 2-bottle choice test following adrenalectomy and consequently bodily sodium depletion. More recently, Robinson and Berridge (2013) have shown that this immediate increase in salt-seeking behavior occurs to discrete salt-paired cues following sodium depletion in the absence of salt before it has been tasted as a desirable reward. In addition, adaptive salt-seeking has also been observed with contextual cues following sodium depletion (Stouffer and White, 2005).

In the brain, there is clear evidence that the central nucleus of the amygdala (Galaverna et al., 1993; Seeley et al., 1993; Tandon et al., 2012; Hu et al., 2015), lateral hypothalamus (Wolf and Quartermain, 1967; Tandon et al., 2012), and the nucleus accumbens (Roitman et al., 2002; Voorhies and Bernstein, 2006; Loriaux et al., 2011; Tandon et al., 2012) are important for the consumption of salt following sodium depletion in order for animals to replenish the deficit. However, there has been surprisingly little work done on the neural circuitry mediating cue-driven salt seeking following sodium depletion. In other words, it is mostly unclear how the brain enables animals to seek out salt in a novel deprivation state. In a recent study, we showed that the ventral pallidum (VP) plays an important role in this phenomenon (Chang et al., 2017). The VP has previously been shown to track the changes in value of salt-paired cues before and after sodium depletion (Tindell et al., 2009; Robinson and Berridge, 2013). However, it was previously unknown whether the VP is necessary for mediating salt appetite in terms of cue-driven salt seeking or salt consumption. Using a novel CPP procedure, described here, we showed that optogenetic inhibition of the VP impairs context-driven salt seeking but not the consumption of salt itself following sodium depletion (Chang et al., 2017).

The protocol we have used to demonstrate this effect allows for not only optogenetics to be used but also other techniques to manipulate the brain (e.g., DREADDs, intracranial injections, lesions) or to record brain activity (e.g., electrophysiology, calcium imaging). Further study of context-driven salt seeking with this procedure may help elucidate the neural bases of disorders of aberrant motivation that may lead to reduced reward seeking, as in depression, or non-homeostatic reward seeking (e.g., overeating leading to obesity). In addition, this procedure could be easily extended to investigate the neural bases of other nutrient deficit-induced changes in behavior such as calcium appetite (Leshem et al., 1999; Schulkin, 2000).