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

Máté Durst, Katalin Könczöl, Tamás Balázsa, Mark D. Eyre, Z. Tóth

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background/objectives: Dysfunction 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/methods: Intrauterine 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. Results: A 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. Conclusions: Sensitivity 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.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalInternational Journal of Obesity
DOIs
Publication statusAccepted/In press - Jun 15 2018

Fingerprint

Lateral Hypothalamic Area
Nucleus Accumbens
Reward
Eating
Milk
Neurons
Hyperphagia
Food
Consummatory Behavior
Obesity
Overnutrition
Ventral Tegmental Area
Proteins
Dopamine Receptors
Tyrosine 3-Monooxygenase
Malnutrition
Causality
Wistar Rats
Young Adult

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Reward-representing D1-type neurons in the medial shell of the accumbens nucleus regulate palatable food intake. / Durst, Máté; Könczöl, Katalin; Balázsa, Tamás; Eyre, Mark D.; Tóth, Z.

In: International Journal of Obesity, 15.06.2018, p. 1-11.

Research output: Contribution to journalArticle

@article{93fafc11cb22429fbd60bc63f01d1085,
title = "Reward-representing D1-type neurons in the medial shell of the accumbens nucleus regulate palatable food intake",
abstract = "Background/objectives: Dysfunction 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/methods: Intrauterine 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. Results: A 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. Conclusions: Sensitivity 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.",
author = "M{\'a}t{\'e} Durst and Katalin K{\"o}ncz{\"o}l and Tam{\'a}s Bal{\'a}zsa and Eyre, {Mark D.} and Z. T{\'o}th",
year = "2018",
month = "6",
day = "15",
doi = "10.1038/s41366-018-0133-y",
language = "English",
pages = "1--11",
journal = "International Journal of Obesity",
issn = "0307-0565",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Reward-representing D1-type neurons in the medial shell of the accumbens nucleus regulate palatable food intake

AU - Durst, Máté

AU - Könczöl, Katalin

AU - Balázsa, Tamás

AU - Eyre, Mark D.

AU - Tóth, Z.

PY - 2018/6/15

Y1 - 2018/6/15

N2 - Background/objectives: Dysfunction 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/methods: Intrauterine 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. Results: A 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. Conclusions: Sensitivity 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.

AB - Background/objectives: Dysfunction 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/methods: Intrauterine 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. Results: A 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. Conclusions: Sensitivity 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.

UR - http://www.scopus.com/inward/record.url?scp=85048537255&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85048537255&partnerID=8YFLogxK

U2 - 10.1038/s41366-018-0133-y

DO - 10.1038/s41366-018-0133-y

M3 - Article

AN - SCOPUS:85048537255

SP - 1

EP - 11

JO - International Journal of Obesity

JF - International Journal of Obesity

SN - 0307-0565

ER -