Reward-representing D1-type neurons in the medial shell of the accumbens nucleus regulate palatable food intake

Máté Durst,Tamás Balázsa,Zsuzsanna E Tóth,Mark D Eyre,Katalin Könczöl

doi:10.1038/s41366-018-0133-y

Máté Durst, Tamás Balázsa + Show 3 more

Open Access

https://doi.org/10.1038/s41366-018-0133-y

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Abstract

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.

Highlights

Feeding reward dysregulation is a basic factor in overeating and consequent obesity [1]
The pathway includes D1Rexpressing medium spiny neurons (MSNs) that, upon activation, stop ongoing eating in mice [19]. These D1R+ neurons target the rostral part of the lateral hypothalamus (LH) [20, 21], an area known to be engaged in reward-related food intake regulation [13]
We evaluated the microstructure of reward-related consummatory behavior and analyzed the Fos expression elicited by palatable food in the Nac and the lateral hypothalamic area (LHA)

Summary

Introduction

Feeding reward dysregulation is a basic factor in overeating and consequent obesity [1]. Stopping feeding, which is crucial to prevent overeating, is realized via a pathway originating from the mSh [19, 20]. The pathway includes D1Rexpressing MSNs that, upon activation, stop ongoing eating in mice [19]. These D1R+ neurons target the rostral part of the lateral hypothalamus (LH) [20, 21], an area known to be engaged in reward-related food intake regulation [13]. The lateral hypothalamic area (LHA) target neurons increase their calcium activity during the eating of palatable food, and are distinct from the mostly more caudally located melanin-concentrating hormone (MCH) and orexin producing neurons [21, 22]

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