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  • Addiction, Drugs
  • Information from Lay-Language Summaries is Embargoed Until the Conclusion of the Scientific Presentation

    858—Animal Behavior and Cognition: Prefrontal and Striatal Systems

    Wednesday, November 13, 2013, 1:00 pm - 5:00 pm

    858.03: Ghrelin affects both phasic dopamine and nucleus accumbens neuron responses to food-predictive stimuli

    Location: Halls B-H

    *J. J. CONE, J. D. ROITMAN, M. F. ROITMAN;
    Psychology, Univ. of Illinois At Chicago, Chicago, IL

    Abstract Body: Environmental cues that predict the availability of food exert powerful sway over motivated behavior, often triggering approach and ultimately consumption of food. Central to these processes are the dopamine neurons in the ventral tegmental area (VTA) and one of their targets - the nucleus accumbens (NAc). Brief (phasic) fluctuations in NAc dopamine and in the firing of NAc neurons signal aspects of food reward including the predictive nature of cues and goal-directed behavior aimed at food. However, motivation for food seeking and consumption is dynamic and fluctuates according to physiological state. The peptide ghrelin is peripherally secreted and acts centrally to promote food intake. Here we sought to determine whether ghrelin signaling would influence phasic mesolimbic signaling evoked by food-predictive stimuli. Rats were trained to associate the presentation of a cue (CS+) with the delivery of a sugar pellet. A second cue was not associated with an outcome (CS-). Following training, real-time recordings in the NAc were made in using fast-scan cylic voltammetry for dopamine and multi-wire, single unit electrophysiology for the firing rate of NAc neurons. Ten CS+ and CS- trials were presented before and after an infusion of either ghrelin (1 ug) or saline into the lateral ventricle (LV) ad-lib fed rats. In a second experiment, we infused either saline or the ghrelin receptor antagonist D-[Lys]-GHRP (1 ug) into the LV of food-restricted rats. We found that LV ghrelin significantly increased (Ghrelin: 144.6 +/- 9%; Saline: 99.0 +/- 5%; p<.01), while LV D-[Lys]-GHRP significantly decreased (GHRP: 45.0 +/- 10%; Saline: 99.7 +/- 15%; p<.05), the magnitude of phasic dopamine evoked by the CS+.The firing rates of NAc neurons were also modulated by CS+ presentation (n=3 rats; 15 of 27 recorded neurons). Preliminary findings indicate an enhancement of the CS+ response by ghrelin (113.6 +/- 4% relative to pre-infusion firing rate during the CS+). Our data demonstrate that central ghrelin action is a potent modulator of phasic mesolimbic signaling evoked by food predictive stimuli.

    Lay Language Summary: Our findings suggest that the hormone ghrelin, which is released by the stomach in response to hunger and promotes food intake, increases neural responses to palatable food and cues that predict food in an area of the brain intimately linked to reward and reward-seeking behavior.
    Obesity has become the health issue of our time. Currently over one-third of US adults meet the criteria for obesity. Annually in the U.S., the health care costs of obesity total over $140 billion. Remarkably, an obese individual spends up to $1000 dollars more per year on health care than someone who is of healthy body weight.
    The dramatic rise in obesity has been linked to the widespread prevalence of highly palatable, rewarding foods. Western society is awash in environmental cues like billboards, neon signs, as well as sights and smells of food that predict food availability. These cues hold powerful sway over our behavior and can lead to consumption of food not necessarily because we are hungry, but simply because we find the taste of food rewarding.
    There is growing support for the idea that the problem of obesity is due, at least in part, to areas of the brain associated with reward and reward seeking behaviors. Dopamine neurons and an area of the brain that they innervate called the nucleus accumbens (NAc) play a strong role as experimental manipulation of these areas can promote food intake in the absence of caloric need.
    Food, as well as cues that have come to be associated with food, evoke large increases in dopamine and in the activity of NAc neurons. Given the link between dopamine, the NAc, and food intake, we hypothesized that the hormone ghrelin, which is released in response to hunger, would augment dopamine and NAc activity evoked by food and food-predictive cues. To investigate this, we sampled dopamine concentration in the NAc as well as the activity of individual NAc neurons, in real-time in rats as they were presented with cues that predicted the delivery of a sugary food pellet. We found that ghrelin potently and specifically increased the dopamine and NAc neural responses to food cues and the food itself. Taken together, our data suggests that modulation of dopamine and NAc neuron responses by ghrelin could act to increase the likelihood of approaching and ultimately consuming food.
    Our results provide new insight into the ways in which feeding hormones influence the brain response to food and food cues, particularly in areas of the brain linked to reward seeking. Thus, these data could inform future interventions aimed at the treatment and prevention of obesity.