Endogenous opioids in the nucleus accumbens promote approach to high-fat food in the absence of caloric need
Abstract
When relatively sated, people (and rodents) are still easily tempted to consume calorie-dense foods, particularly those containing fat and sugar. Consumption of such foods while calorically replete likely contributes to obesity. The nucleus accumbens (NAc) opioid system has long been viewed as a critical substrate for this behavior, mainly via contributions to the neural control of consumption and palatability. Here, we test the hypothesis that endogenous NAc opioids also promote appetitive approach to calorie-dense food in states of relatively high satiety. We simultaneously recorded NAc neuronal firing and infused a μ-opioid receptor antagonist into the NAc while rats performed a cued approach task in which appetitive and consummatory phases were well separated. The results reveal elements of a neural mechanism by which NAc opioids promote approach to high-fat food despite the lack of caloric need, demonstrating a potential means by which the brain is biased towards overconsumption of palatable food.
Data availability
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Data from: Endogenous opioids in the nucleus accumbens promote approach to high-fat food in the absence of caloric needAvailable at Dryad Digital Repository under a CC0 Public Domain Dedication.
Article and author information
Author details
Funding
National Institutes of Health (DA019473)
- Saleem M Nicola
Klarman Family Foundation (Pilot Award)
- Saleem M Nicola
Brain and Behavior Research Foundation (NARSAD Young Investigator Awards)
- Saleem M Nicola
National Institutes of Health (DA038412)
- Saleem M Nicola
National Institutes of Health (MH092757)
- Saleem M Nicola
National Institutes of Health (DA041725)
- Saleem M Nicola
Klarman Family Foundation (Two Year Award)
- Saleem M Nicola
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Richard D Palmiter, Howard Hughes Medical Institute, University of Washington, United States
Ethics
Animal experimentation: All procedures involving animals were in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee at Albert Einstein College of Medicine (protocols 20100103, 20130204, and 20160206).
Version history
- Received: January 9, 2018
- Accepted: March 20, 2018
- Accepted Manuscript published: March 27, 2018 (version 1)
- Version of Record published: April 17, 2018 (version 2)
Copyright
© 2018, Caref & Nicola
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Further reading
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- Developmental Biology
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Adolescence is characterized by changes in reward-related behaviors, social behaviors, and decision-making. These behavioral changes are necessary for the transition into adulthood, but they also increase vulnerability to the development of a range of psychiatric disorders. Major reorganization of the dopamine system during adolescence is thought to underlie, in part, the associated behavioral changes and increased vulnerability. Here, we utilized fast scan cyclic voltammetry and microdialysis to examine differences in dopamine release as well as mechanisms that underlie differential dopamine signaling in the nucleus accumbens (NAc) core of adolescent (P28-35) and adult (P70-90) male rats. We show baseline differences between adult and adolescent-stimulated dopamine release in male rats, as well as opposite effects of the α6 nicotinic acetylcholine receptor (nAChR) on modulating dopamine release. The α6-selective blocker, α-conotoxin, increased dopamine release in early adolescent rats, but decreased dopamine release in rats beginning in middle adolescence and extending through adulthood. Strikingly, blockade of GABAA and GABAB receptors revealed that this α6-mediated increase in adolescent dopamine release requires NAc GABA signaling to occur. We confirm the role of α6 nAChRs and GABA in mediating this effect in vivo using microdialysis. Results herein suggest a multisynaptic mechanism potentially unique to the period of development that includes early adolescence, involving acetylcholine acting at α6-containing nAChRs to drive inhibitory GABA tone on dopamine release.
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- Neuroscience
Dopamine axons are the only axons known to grow during adolescence. Here, using rodent models, we examined how two proteins, Netrin-1 and its receptor, UNC5C, guide dopamine axons toward the prefrontal cortex and shape behaviour. We demonstrate in mice (Mus musculus) that dopamine axons reach the cortex through a transient gradient of Netrin-1-expressing cells – disrupting this gradient reroutes axons away from their target. Using a seasonal model (Siberian hamsters; Phodopus sungorus) we find that mesocortical dopamine development can be regulated by a natural environmental cue (daylength) in a sexually dimorphic manner – delayed in males, but advanced in females. The timings of dopamine axon growth and UNC5C expression are always phase-locked. Adolescence is an ill-defined, transitional period; we pinpoint neurodevelopmental markers underlying this period.