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Sweetened-fat intake sensitizes gamma-aminobutyric acid-mediated feeding responses elicited from the nucleus accumbens shell.

ABSTRACT: There is much interest in exploring whether reward-driven feeding can produce druglike plasticity in the brain. The gamma-aminobutyric acid (GABA) system in the nucleus accumbens (Acb) shell, which modulates hypothalamic feeding systems, is well placed to "usurp" homeostatic control of feeding. Nevertheless, it is unknown whether feeding-induced neuroadaptations occur in this system.Separate groups of ad libitum-maintained rats were exposed to daily bouts of sweetened-fat intake, predator stress, or intra-Acb shell infusions of either d-amphetamine (2 or 10 ?g) or the ?-opioid agonist D-[Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO, 2.5 ?g), then challenged with intra-Acb shell infusion of the GABAA agonist, muscimol (10 ng).Exposure to sweetened fat robustly sensitized muscimol-induced feeding. Sensitization was present 1 week after cessation of the palatable feeding regimen but had abated by 2 weeks. Rats exposed to sweetened fat did not show an altered feeding response to food deprivation. Repeated intra-Acb shell infusions of DAMGO (2.5 ?g) also sensitized intra-Acb shell muscimol-driven feeding. However, neither repeated intra-Acb shell d-amphetamine infusions (2 or 10 ?g) nor intermittent exposure to an aversive stimulus (predator stress) altered sensitivity to muscimol.Palatable feeding engenders hypersensitivity of Acb shell GABA responses; this effect may involve feeding-induced release of opioid peptides. Heightened arousal, aversive experiences, or increased catecholamine transmission alone are insufficient to produce the effect, and a hunger-induced feeding drive is insufficient to reveal the effect. These findings reveal a novel type of food-induced neuroadaptation within the Acb; possible implications for understanding crossover effects between food reward and drug reward are discussed.

SUBMITTER: Newman S

PROVIDER: S-EPMC3885159 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Sweetened-fat intake sensitizes gamma-aminobutyric acid-mediated feeding responses elicited from the nucleus accumbens shell.

Newman Sarah S Pascal Lindsay L Sadeghian Ken K Baldo Brian A BA

Biological psychiatry 20130108 9

<h4>Background</h4>There is much interest in exploring whether reward-driven feeding can produce druglike plasticity in the brain. The gamma-aminobutyric acid (GABA) system in the nucleus accumbens (Acb) shell, which modulates hypothalamic feeding systems, is well placed to "usurp" homeostatic control of feeding. Nevertheless, it is unknown whether feeding-induced neuroadaptations occur in this system.<h4>Methods</h4>Separate groups of ad libitum-maintained rats were exposed to daily bouts of sw ...[more]

PMID: 23312563

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Project description:Background/objectivesDysfunction in reward-related aspects of feeding, and consequent overeating in humans, is a major contributor to obesity. Intrauterine undernutrition and overnutrition are among the predisposing factors, but the exact mechanism of how overeating develops is still unclear. Consummatory behavior is regulated by the medial shell (mSh) of the accumbens nucleus (Nac) through direct connections with the rostral part of the lateral hypothalamic area (LHA). Our aim was to investigate whether an altered Nac-LHA circuit may underlie hyperphagic behavior.Subjects/methodsIntrauterine protein-restricted (PR) male Wistar rats were used as models for hyperphagia. The experiments were performed using young adult control (normally nourished) and PR animals. Sweet condensed milk (SCM) served as a reward to test consumption and subsequent activation (Fos+) of Nac and LHA neurons. Expression levels of type 1 and 2 dopamine receptors (D1R, D2R) in the Nac, as well as tyrosine hydroxylase (TH) levels in the ventral tegmental area, were determined. The D1R agonist SKF82958 was injected into the mSh-Nac of control rats to test the effect of D1R signaling on SCM intake and neuronal cell activation in the LHA.ResultsA group of food reward-representing D1R+ neurons was identified in the mSh-Nac. Activation (Fos+) of these neurons was highly proportional to the consumed palatable food. D1R agonist treatment attenuated SCM intake and diminished the number of SCM-activated cells in the LHA. Hyperphagic PR rats showed increased intake of SCM, reduced D1R expression, and an impaired response to SCM-evoked neuronal activation in the mSh-Nac, accompanied by an elevated number of Fos+ neurons in the LHA compared to controls.ConclusionsSensitivity of food reward-representing neurons in the mSh-Nac determines the level of satisfaction that governs cessation of consumption, probably through connections with the LHA. D1R signaling is a key element in this function, and is impaired in obesity-prone rats.

Project description:BackgroundThe nucleus accumbens (NAc) is an important region in motivation and reward. Glutamatergic inputs from the infralimbic cortex (ILC) to the shell region of the NAc (NAcSh) have been implicated in driving the motivation to seek reward through repeated action-based behavior. While this has primarily been studied in males, observed sex differences in motivational circuitry and behavior suggest that females may be more sensitive to rewarding stimuli. These differences have been implicated for the observed vulnerability in women to substance use disorders.MethodsWe used an optogenetic self-stimulation task in addition to ex vivo electrophysiological recordings of NAcSh neurons in mouse brain slices to investigate potential sex differences in ILC-NAcSh circuitry in reward-seeking behavior. Glutamatergic neurons in the ILC were infected with an AAV delivering DNA encoding for channelrhodopsin. Entering the designated active corner of an open field arena resulted in photostimulation of the ILC terminals in the NAcSh. Self-stimulation occurred during two consecutive days of testing over three consecutive weeks: first for 10 Hz, then 20 Hz, then 30 Hz. Whole-cell recordings of medium spiny neurons in the NAcSh assessed both optogenetically evoked local field potentials and intrinsic excitability.ResultsAlthough both sexes learned to seek the active zone, within the first day, females entered the zone more than males, resulting in a greater amount of photostimulation. Increasing the frequency of optogenetic stimulation amplified female reward-seeking behavior. Males were less sensitive to ILC stimulation, with higher frequencies and repeated days required to increase male reward-seeking behavior. Unexpectedly, ex vivo optogenetic local field potentials in the NAcSh were greater in slices from male animals. In contrast, female medium-spiny neurons (MSNs) displayed significantly greater intrinsic neuronal excitability.ConclusionsTaken together, these data indicate that there are sex differences in the motivated behavior driven by glutamate within the ILC-NAcSh circuit. Though glutamatergic signaling was greater in males, heightened intrinsic excitability in females appears to drive this sex difference.

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Sweetened-fat intake sensitizes gamma-aminobutyric acid-mediated feeding responses elicited from the nucleus accumbens shell.

Publications

Sweetened-fat intake sensitizes gamma-aminobutyric acid-mediated feeding responses elicited from the nucleus accumbens shell.

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