Modulation of food reward by adiposity signals
Introduction
The ability of nutritional status to modulate performance in behavioral tasks that assess reinforcement, motivation, or reward has been well-appreciated for many decades. Almost exclusively, studies have focused on the generalized outcome that food restriction or food deprivation results in enhanced performance in behavioral paradigms. Although examples of this are too numerous to be described completely here, the reader is directed to recent reviews [1], [2], [3]. Observations from these studies include increased self-administration of several classes of addictive drugs (cocaine, amphetamine, opioids, etc) [4]; enhanced relapse to drug taking [5]; decreased threshold for lateral hypothalamic self-stimulation [6], [7]; and cocaine-conditioned place preference [8]. Since each of these behavioral paradigms utilizes a somewhat different subset of CNS circuitry, and evaluates different aspects of motivation or reinforcement, such results argue for a very strong interaction between brain reward circuitry, and the CNS circuitry which regulates nutritional status and energy homeostasis. The anatomical and neurochemical correlates of this altered behavioral sensitivity have begun to be elucidated: Increased dopamine release within the nucleus accumbens (Nacc) [9]; altered re-uptake of dopamine in the Nacc (a paradigm-dependent observation [10], [11], [12]); and downstream sequelae of dopamine receptor activation in the Nacc have been the most intensely investigated possibilities [13]. Altered activity in specific brain opioidergic circuitry may be involved as well [14].
Food is a naturally rewarding and motivating stimulus and, perhaps not surprisingly, behavioral performance in tasks where food is the reward is enhanced by food restriction or deprivation. Self-stimulation within certain lateral hypothalamic sites induces an eating response, and self-stimulation-induced feeding is augmented with food restriction [15]. Likewise, the ability of food to condition a place preference, or self-administration of food, is increased with food deprivation [16], [17], [18], [19], [20]. Since peripherally-derived signals of body adiposity or energy homeostasis, i.e., the pancreatic hormone insulin and the adipose-derived hormone leptin, have been shown to act within the CNS [21], their role in mediating the effect of food restriction on motivational behaviors has been investigated [1]. Both insulin and leptin administered intracerebroventricularly (ICV) can reverse the shifted threshold of lateral hypothalamic self-stimulation following food restriction [22], [23]. ICV leptin also reverses food-restriction-enhanced relapse to heroin self-administration [5]. Finally, peripheral leptin replacement reverses food-restriction-induced conditioning of place preference by sucrose [24]. It should be emphasized that the underlying significance of all of these studies lies not solely in the demonstration that these candidate adiposity signals regulate food reward, but in the generalization that can be derived from these findings: Any neuroendocrine signal, peripherally or centrally derived, may be a candidate for modulation of food reward and this hypothesis can be systematically evaluated by taking advantage of well-characterized behavioral paradigms to start to discern which components of reward and motivation are being affected. The orexigenic peptide ghrelin, for example, can stimulate feeding when administered into the ventral tegmental area (VTA) [25], a major dopaminergic nucleus and critical center of motivational circuitry within the CNS [26].
Section snippets
Insulin, leptin, and food reward
Of particular interest to us is the phenomenon of palatable food intake in the face of caloric repletion. In “Westernized” societies caloric intake is chronically excessive, and this is due in part to the unlimited availability of inexpensive, highly palatable, highly calorically dense food [27]. Thus, while it is possible that the enhanced rewarding or motivating values of food with food restriction or deprivation may reflect what happens during dietary cycling and bingeing, we consider it
CNS sites of action for adiposity signal modulation of food reward
We have begun to explore the specific CNS location(s) whereby insulin and leptin may decrease food reward, based on our studies of ICV administration. A minimum set of criteria for identifying target sites would have to include the expression of receptors for insulin or leptin, and functional activity of these receptors demonstrated at both the cellular and behavioral level. We have obtained evidence which suggests that the VTA may serve as a direct target for insulin and leptin action. Using
New directions: modulation of food reward and reinforcement by baseline diet experience, age, and type of food reward
As we and others have begun to establish that adiposity signals and other CNS energy-regulatory signals may modulate food reward, it is becoming important to put these effects within the context of normal events within daily life and the life cycle. We base this perspective on both studies within obesity research which have clearly demonstrated that diet composition, concomitant with or independent of consequent obesity, can impact on the efficacy of insulin and leptin energy-regulatory effects
Future directions for food reward research
An important challenge awaits investigators of food reward and its potential regulation or modulation. While we are gaining ground on understanding some basic aspects of food reward within a defined physiological context, we need to simultaneously be aware of the greater complexities which may arise in real life situations for people, if we hope to utilize our knowledge for any sort of helpful therapeutic direction (i.e., pharmaceutical or behavioral intervention). For example, food reward is
Acknowledgments
Dianne Figlewicz Lattemann is a Research Career Scientist and recipient of Merit Review funding from the Dept of Veterans Affairs. The studies described here were supported by NIH RO1DK 40963 and NIH 5P20RR020774. Amy MacDonald Naleid is supported by the University of Washington NIH Training Grant T32-AA007455. Alfred J. Sipols is supported by Latvian Council of Science Grant 04.1116. We gratefully acknowledge the discussion, advice, and support from Drs. Yavin Shaham and Jeff Grimm for the
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2019, Physiology and BehaviorCitation Excerpt :Indeed, metabolic factors such as insulin, leptin, glucagon-like peptide-1 (GLP-1) and amylin inhibit VTA dopamine neurons and decrease food intake [64,72]. Furthermore, central administration of both leptin and insulin are known to decrease striatal dopamine release as well as act directly on dopamine neurons to regulate food intake [68,73–75]. In contrast, the feeding hormone ghrelin promotes ad libitum food intake through actions on ghrelin receptors expressed in the VTA and nucleus accumbens [76,77].
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