Kelley AE, Baldo BA, Pratt WE, Will MJ. Corticostriatal-hypothalamic circuitry and food motivation: Integration of energy, action and reward. Physiol Behav 86: 773-795

Department of Psychiatry, University of Wisconsin-Madison Medical School, 6001 Research Park Blvd., Madison, WI 53719, USA.
Physiology & Behavior (Impact Factor: 2.98). 01/2006; 86(5):773-95. DOI: 10.1016/j.physbeh.2005.08.066
Source: PubMed


Work over the past decade has supported the idea that discrete aspects of appetitive motivation are differentially mediated by separate but interacting neurochemical systems within the nucleus accumbens (Acb). We review herein a series of studies in rats comparing the effects of manipulating Acb amino acid, opioid, acetylcholine, and dopamine systems on tests of free-feeding and food-reinforced operant responding. Results from our laboratory and in the literature support three general conclusions: (1) GABA output neurons localized exclusively within the Acb shell directly influence hypothalamic effector mechanisms for feeding motor patterns, but do not participate in the execution of more complex food-seeking strategies; (2) enkephalinergic neurons distributed throughout the Acb and caudate-putamen mediate the hedonic impact of palatable (high sugar/fat) foods, and these neurons are under modulatory control by striatal cholinergic interneurons; and (3) dopamine transmission in the Acb governs general motoric and arousal processes related to response selection and invigoration, as well as motor learning-related plasticity. These dissociations may reflect the manner in which these neurochemical systems differentially access pallido-thalamo-cortical loops reaching the voluntary motor system (in the case of opioids and dopamine), versus more restricted efferent connections to hypothalamic motor/autonomic control columns (in the case of Acb shell GABA and glutamate systems). Moreover, we hypothesize that while these systems work in tandem to coordinate the anticipatory and consummatory phases of feeding with hypothalamic energy-sensing substrates, the striatal opioid network evolved a specialized capacity to promote overeating of energy-dense foods beyond acute homeostatic needs, to ensure an energy reserve for potential future famine.

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    • "Consistent with these pharmacological studies, unit recordings in freely feeding rats have identified subpopulations of NAcSh neurons that reduce their activity during feeding (Krause et al., 2010; Roitman et al., 2010; Tellez et al., 2012) and that shift to increased firing when animals are presented with aversive conditioned food (Roitman et al., 2010). From these studies, a model has been proposed in which inhibitory projections from the NAcSh to the LH serve as a sensory sentinel, allowing rapid control over food consumption in response to motivational or sensory signals (Baldo and Kelley, 2007; Kelley et al., 2005b). However, this circuit has not been resolved at the cellular level and its temporal dynamics have not been characterized. "
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    ABSTRACT: Feeding satisfies metabolic need but is also controlled by external stimuli, like palatability or predator threat. Nucleus accumbens shell (NAcSh) projections to the lateral hypothalamus (LH) are implicated in mediating such feeding control, but the neurons involved and their mechanism of action remain elusive. We show that dopamine D1R-expressing NAcSh neurons (D1R-MSNs) provide the dominant source of accumbal inhibition to LH and provide rapid control over feeding via LH GABA neurons. In freely feeding mice, D1R-MSN activity reduced during consumption, while their optogenetic inhibition prolonged feeding, even in the face of distracting stimuli. Conversely, activation of D1R-MSN terminals in LH was sufficient to abruptly stop ongoing consumption, even during hunger. Direct inhibition of LH GABA neurons, which received input from D1R-MSNs, fully recapitulated these findings. Together, our study resolves a feeding circuit that overrides immediate metabolic need to allow rapid consumption control in response to changing external stimuli.
    Neuron 11/2015; 88(3):553–564. DOI:10.1016/j.neuron.2015.09.038 · 15.05 Impact Factor
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    • "For example, it has already been shown that CeA activity is required to observe feeding driven by an energy deficit (24-hr food deprivation) (Baldo, Alsene, Negron, & Kelley, 2005; Minano, Meneres Sancho, Sancibrian, Salinas, & Myers, 1992). Furthermore, inactivation of the CeA, but not the BLA, blocks intra-Acb muscimolinduced feeding (Baldo et al., 2005), a pharmacological model that parallels the motivational state induced by energy deficit (i.e., food restriction; see Kelley et al., 2005, for review). "

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    • "To relate the behavioral studies to neural activity, we recorded the responses to DEP20 in the NAc shell, a brain region involved in reward, feeding, and motor activity (Brown et al. 2011; Kelley et al. 2005; Li et al. 2012 "
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    ABSTRACT: Obesity is a worldwide health problem that has reached epidemic proportions. To ameliorate this problem, one approach is the use of appetite suppressants. These compounds are frequently amphetamine congeners such as diethylpropion (DEP), phentermine (PHEN), and bupropion (BUP), whose effects are mediated through serotonin, norepinephrine, and dopaminergic pathways. The nucleus accumbens (NAc) shell receives dopaminergic inputs and is involved in feeding and motor activity. However, little is known about how appetite suppressants modulate its activity. Therefore, we characterized behavioral and neuronal NAc shell responses to short-term treatments of DEP, PHEN, and BUP. These compounds caused a transient decrease in weight and food intake while increasing locomotion, stereotypy, and insomnia. They evoked a large inhibitory imbalance in NAc shell spiking activity that correlated with the onset of locomotion and stereotypy. Analysis of the local field potentials (LFPs) showed that all three drugs modulated beta, theta, and delta oscillations. These oscillations do not reflect an aversive-malaise brain state, as ascertained from taste aversion experiments, but tracked both the initial decrease in weight and food intake and the subsequent tolerance to these drugs. Importantly, the appetite suppressant-induced weight loss and locomotion were markedly reduced by intragastric (and intra-NAc shell) infusions of dopamine antagonists SCH-23390 (D1 receptor) or raclopride (D2 receptor). Furthermore, both antagonists attenuated appetite suppressant-induced LFP oscillations and partially restored the imbalance in NAc shell activity. These data reveal that appetite suppressant-induced behavioral and neuronal activity recorded in the NAc shell depend, to various extents, on dopaminergic activation and thus point to an important role for D1/D2-like receptors (in the NAc shell) in the mechanism of action for these anorexic compounds.
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