Genetic, Motivational, and Metabolic Factors Modulate the Neural Drive To Maintain Body Weight
Barry Levin, M.D.

[Slides not available.]

SUMMARY: Dr. Barry Levin used rat studies to show that the brain controls behavioral, neuroendocrine, and metabolic systems that regulate the level of defended body fat, and that body weight is dependent upon a complex interaction among motivational, metabolic, and developmental factors imposed by the environment upon specific sets of interconnected, but separate plastic neural systems. Levin explained that rats with a genetic predisposition to develop diet-induced obesity (DIO) share many characteristics with polygenic forms of human obesity where increased dietary fat produces obesity and insulin resistance. Once rats develop DIO, the central and peripheral systems controlling energy homeostasis “reset” and they avidly defend their increased adiposity. This type of obesity and the neural systems regulating it are dependent on the adipose-derived hormone leptin, and DIO rats have an inborn reduction in their sensitivity to the catabolic effects of leptin. Levin also discussed leptin-independent neural pathways that respond to diet palatability and the manipulation of dietary availability, content, and palatability for producing long-term, genotype-dependent reorganization of neural pathways involved in energy homeostasis.

Cortico-Striatal-Hypothalamic Networks and Motivation for Food: Integration of Cognition, Reward, and Energy
Ann E. Kelley, Ph.D.

SUMMARY: The neural circuits affected by rewarding drugs and presumed to be profoundly altered in addiction are the very pathways that control intake of our most vital natural reward, food. Dr. Ann Kelley has been exploring the role of neurotransmitter systems within the nucleus accumbens, a brain region implicated in natural reward processes as well as addiction, in the control of food motivation and intake. Her research team examined local GABAergic, dopaminergic, and opioid peptide systems as well as the influence of input and output structures such as the amygdala and lateral hypothalamus. Their work has shown that these neurochemical systems play specific and dissociable roles in different aspects of food seeking and food intake. The influence of central and basolateral amygdala, as well as lateral hypothalamus, in regulating accumbens reward mechanisms appears particularly critical. Kelley proposes that the nucleus accumbens integrates information related to cognitive and emotional processing with hypothalamic mechanisms mediating energy balance and that this system as a whole enables complex hierarchical control of adaptive ingestive behavior.

Food and Drug Cravings: Metaphor or Common Mechanisms?
Marcia L. Pelchat, Ph.D.

SUMMARY: The objective of Dr. Marcia Pelchat’s presentation was to provide a better understanding of neural mechanisms for food cravings and to review the evidence for common mechanisms for desires of all kinds, whether healthy or pathological. Her literature review involved studies on the effects of neurotransmitters (including endogenous opiates, serotonin, and GABA) on ingestive behavior and drug cravings; and recent neuroimaging studies on drug and alcohol craving and on feeding and the chemical senses. Pelchat also summarized data from her laboratory on food craving in cocaine addicts as well as an fMRI study of food cravings in healthy adults. Taken together, the facts support the hypothesis that there are common brain mechanisms for food and for drug cravings. Such knowledge could prove to be useful in the development of treatments for both substance abuse and eating disorders.

Common and Diverging Neurobiological Features of Feeding and Drug Self-Administration in Humans
Dana M. Small, Ph.D.

SUMMARY: Feeding and drug self-administration share many common neural substrates, but there appear to be important differences between the brain mechanisms supporting adaptive and nonadaptive ingestive behaviors. Dr. Dana Small reported on findings from a series of neuroimaging studies to elucidate brain mechanisms of food reward in healthy human volunteers. Taken in conjunction with other findings in the literature, results suggest there is considerable overlap between brain activation produced by drugs of abuse and a highly palatable food (e.g., chocolate). However, dissociations are also evident. Consumption of a drug has been shown to lead to dopamine release in the ventral striatum, whereas consumption of a favorite food leads to dopamine release in the dorsal striatum. Moreover, dopamine release in response to drugs is correlated with degree of drug wanting, whereas dopamine release in response to feeding is related to perceived meal pleasantness and not to desire to eat or degree of hunger or satiation.

Obesity and Addiction: Neuroimaging Studies
Gene-Jack Wang, M.D.

SUMMARY: Dr. Gene-Jack Wang conducted neuroimaging studies to implicate the involvement of brain dopamine (DA) in normal and pathological food intake in humans. In normal body weight fasting subjects, food presentation that could not be consumed was associated with increases in striatal extracellular DA, which provides evidence of an involvement of DA in nonhedonic motivational properties of food intake. In pathologically obese subjects, Wang found reductions in striatal DA D2 receptors similar to that in drug-addicted subjects, as well as increased metabolism in the somatosensory cortex. In the case of obese individuals, the reduction in receptors coupled with the enhanced sensitivity to food palatability puts them at risk for food overconsumption as their most salient reinforcer.