Both preclinical and clinical studies have identified a dist

Both preclinical and clinical studies have identified a distributed set of CNS nuclei that participate in cognitive control of feeding behavior. Preclinical studies that utilize restricted access feeding schedules (RFS) indicate that rodents learn to anticipate delivery of scheduled meals as indicated by increased locomotor activity prior to meal delivery (Poulin and Timofeeva, 2008). RFS models typically utilize a 20hr deprivation, 4hr feeding access paradigm. In this model rats are calorically restricted (CR) from food for 20 h and allowed to feed for 4 h per day. Rats initially loose weight on RFS schedules but gradually learn to anticipate meal delivery to allow ingestion of a large caloric load in a short period of time and increase body weight. RFS based feeding models critical aspects of dieting as it stimulates acquisition of cues that signal food availability in the context of restriction. This ability to anticipate scheduled meals is referred to as food entrainable oscillation (FEO). FEO is associated with activation of the hippocampus (Hp), medial prefrontal cortex (mPFC), nucleus accumbens (NAc), ventral tegmental area (VTA), arcuate (Arc), and dorsomedial (DMH) nucleus of the hypothalamus (Poulin and Timofeeva, 2008). Numerous lesions studies have failed to determine one single Disuflo Cy3 azide synthesis region in this network that reduces FEO suggesting that this behavior is controlled by distributed activity within this network. In contrast to RFS, restricted access to palatable meals (RPM) in non-restricted (NR) rats leads to activation of the mPFC, VTA, NAc, and the Arc (Blancas et al., 2014). Notably, neural activation persists even when rodents are no longer maintained RPM schedules indicating that activation of brain reward circuits may serve a time keeping function for hedonic food intake. In this context, clinical imaging experiments indicate that the visual presentation of palatable food cues in non-restricted patients activates a forebrain network of CNS regions including the frontal cortex, amygdala (AMG), striatum and midbrain (Grill et al., 2007, Ng et al., 2011, O’Doherty et al., 2002, Siep et al., 2009, Stice et al., 2008). Importantly, beyond FEO, presentation of food cues stimulates feeding in behaviorally sated rodents and also activates this forebrain network (Petrovich, 2011, Petrovich et al., 2005). Inactivation of the frontal cortex, amygdala, or functional disconnection of the amygdala from the lateral hypothalamus (LH) attenuates the ability of cues to stimulate feeding in sated rodents (Petrovich et al., 2005). Moreover, pharmacological activation of the frontal cortex leads to binge type intake of palatable food, an effect that correlates with increased neuronal activation of the LH (Mena et al., 2013, Blasio et al., 2014). This collection of preclinical and clinical studies indicates that cognitive-emotional (mPFC, AMG), and reward regions (NAc) communicate with homoeostatic centers (Arc, LH) to control feeding in the absence of caloric need. Although we have increased our understanding regarding the neural substrates involved in cognitive feeding, we still do not understand 1) how this network is activated, or 2) once activated, how this network overrides homeostatic controls to induce feeding in the absence of caloric need. Specifically, we do not know which hormones or transmitter systems participate in these processes, how learning alters activity of these factors, when or where such factors are released, or how they interact with the CNS to control feeding behavior. The first step is to identify processes that promote anticipation for palatable food, because without that, sustained increases in meal size are unlikely to persist. Emerging evidence indicates that the GI peptide ghrelin is a key regulator of food anticipation and hedonic food intake, making it a likely candidate to link learning, anticipation and hunger with overconsumption of palatable food.