We elaborate herein a novel theory of basal ganglia function that accounts for why palatable, energy-dense foods retain high incentive value even when immediate physiological energy requirements have been met. Basal ganglia function has been studied from the perspective of topographical segregation of processing within parallel circuits, with primary focus on motor control and cognition. Recent findings suggest, however, that the striatum can act as an integrated unit to modulate motivational state. We describe evidence that the striatal enkephalin system, which regulates the hedonic impact of preferred foods, undergoes coordinated gene expression changes that track current motivational state with regard to food intake. Striatal enkephalin gene expression is also downregulated by an intrastriatal infusion of a cholinergic muscarinic antagonist, a manipulation that greatly suppresses food intake. To account for these findings, we propose that signaling through a hypothalamic-midline thalamic-striatal axis impinges on the cholinergic interneurons of the striatum, which via their large, overlapping axonal fields act as a network to modulate enkephalin-containing striatal output neurons. A key relay in this circuit is the paraventricular thalamic nucleus, which receives convergent input from orexin-coded hypothalamic energy-sensing and behavioral state-regulating neurons, as well as from circadian oscillators, and projects to cholinergic interneurons throughout the striatal complex. We hypothesize that this system evolved to coordinate feeding and arousal, and to prolong the feeding central motivational state beyond the fulfillment of acute energy needs, thereby promoting "overeating" and the consequent development of an energy reserve for potential future food shortages.
One of the defining characteristics of the research of Ann E. Kelley was her recognition that the neuroscience underlying basic learning and motivation processes also shed significant light upon mechanisms underlying drug addiction and maladaptive eating patterns. In this review, we examine the parallels that exist in the neural pathways that process both food and drug reward, as determined by recent studies in animal models and human neuroimaging experiments. We discuss contemporary research that suggests that hyperphagia leading to obesity is associated with substantial neurochemical changes in the brain. These findings verify the relevance of reward pathways for promoting consumption of palatable, calorically dense foods, and lead to the important question of whether changes in reward circuitry in response to intake of such foods serve a causal role in the development and maintenance of some cases of obesity. Finally, we discuss the potential value for future studies at the intersection of the obesity epidemic and the neuroscience of motivation, as well as the potential concerns that arise from viewing excessive food intake as an “addiction”. We suggest that it might be more useful to focus on overeating that results in frank obesity, and multiple health, interpersonal, and occupational negative consequences as a form of food “abuse”.
These experiments tested whether nucleus accumbens muscarinic or nicotinic acetylcholine receptor activation is required for rats to learn to lever press for sucrose. Muscarinic blockade with scopolamine (1.0 microg/side or 10.0 microg/side), but not nicotinic antagonism with mecamylamine (10.0 microg/side), inhibited learning and performance when applied to the core or shell. Further experiments showed that acute accumbens scopolamine treatment increased locomotor activity and reduced sucrose consumption. However, microanalyses of behavioral events in the instrumental chamber revealed that reductions of lever press performance during muscarinic blockade were not due to gross motor dysfunction. Accumbens core scopolamine was subsequently shown to reduce the amount of work rats would expend under a progressive ratio paradigm. These novel results implicate nucleus accumbens muscarinic receptors in the modulation of appetitive learning, performance, and motivation for food.
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