Customized DNA–directed precision nutrition to balance the brain reward circuitry and reduce addictive behaviors

AbstractThe Brain Reward Cascade (BRC) is an interaction of neurotransmitters and their respective genes to control the amount of dopamine released within the brain. Any variations within this pathway, whether genetic or environmental (epigenetic), may result in addictive behaviors as well as altered pain tolerance. While there are many studies claiming a genetic association with addiction and other behavioral infractions, defined as Reward Deficiency Syndrome (RDS), not all are scientifically accurate and in some case just wrong. Albeit our bias, we discuss herein the facts and fictions behind molecular genetic testing in RDS (including pain and addiction) and the significance behind the development of the Genetic Addiction Risk Score (GARSPREDX™), the first test to accurately predict one’s genetic risk for RDS.

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Neurogenetics and Clinical Evidence for the Putative Activation of the Brain Reward Circuitry by a Neuroadaptagen: Proposing an Addiction Candidate Gene Panel Map

Journal of Psychoactive Drugs ◽

10.1080/02791072.2011.587393 ◽

2011 ◽

Vol 43 (2) ◽

pp. 108-127 ◽

Cited By ~ 21

Author(s):

Thomas J.H. Chen ◽

Kenneth Blum ◽

Amanda L.C. Chen ◽

Abdalla Bowirrat ◽

William B. Downs ◽

...

Keyword(s):

Candidate Gene ◽

Clinical Evidence ◽

Gene Panel ◽

Reward Circuitry ◽

Brain Reward ◽

The Brain

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Brain Site-Specific Inhibitory Effects of the GLP-1 Analogue Exendin-4 on Alcohol Intake and Operant Responding for Palatable Food

International Journal of Molecular Sciences ◽

10.3390/ijms21249710 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9710

Author(s):

Kayla J. Colvin ◽

Henry S. Killen ◽

Maxwell J. Kanter ◽

Maximilian C. Halperin ◽

Liv Engel ◽

...

Keyword(s):

Alcohol Intake ◽

Critical Role ◽

Addictive Behaviors ◽

Receptor Signaling ◽

Palatable Food ◽

Sprague Dawley ◽

Inhibitory Effects ◽

Operant Responding ◽

Brain Reward ◽

The Brain

Approximately 14.4 million Americans are experiencing alcohol use disorder (AUD) and about two-thirds of people who experience drug addiction will relapse, highlighting the need to develop novel and effective treatments. Glucagon-like peptide-1 (GLP-1) is a peptide hormone implicated in the mesocorticolimbic reward system and has become a peptide of interest with respect to its putative inhibitory effects on drug reward. In order to further develop treatments for those diagnosed with AUD, the interplay between GLP-1 receptor signaling and ethanol consumption must be elucidated. In the present study, we investigated the ability of the GLP-1 analogue, exendin-4 (Ex-4), to alter alcohol intake and operant responding for sucrose pellets in order to further understand the role of this compound in mediating reward. We selected multiple sites throughout the prosencephalic and mesencephalic regions of the brain, where we directly administered various doses of Ex-4 to male Sprague Dawley rats. In alcohol investigations, we utilized a two-bottle choice intermittent access protocol. In separate groups of rats, we adopted an operant paradigm in order to examine the effect of Ex-4 on motivated responding for palatable food. Results indicated that GLP-1 receptor signaling effectively suppressed voluntary alcohol intake when injected into the ventral tegmental area (VTA), the accumbens core (NAcC) and shell (NAcS), the dorsomedial hippocampus (DMHipp), and the lateral hypothalamus (LH), which are all structures linked to brain reward mechanisms. The arcuate nucleus (ARcN) and the paraventricular nucleus (PVN) of the hypothalamus were unresponsive, as was the basolateral amygdala (BLA). However, Ex-4 treatment into the ArcN and PVN suppressed operant responding for sucrose pellets. In fact, the VTA, NAcC, NAcS, LH, and the DMHipp all showed comparable suppression of sucrose responding. Overall, our findings suggest that these central structures are implicated in brain reward circuitry, including alcohol and appetitive motivation, which may be mediated by GLP-1 receptor mechanisms. GLP-1, therefore, may play a critical role in modifying addictive behaviors via activation of multiple GLP-1 systems throughout the brain.

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The effect of dopamine transporter blockade on optical self-stimulation: behavioral and computational evidence for parallel processing in brain reward circuitry

10.1101/867481 ◽

2019 ◽

Author(s):

Ivan Trujillo-Pisanty ◽

Kent Conover ◽

Pavel Solis ◽

Daniel Palacios ◽

Peter Shizgal

Keyword(s):

Dopamine Transporter ◽

Time Allocation ◽

Opportunity Cost ◽

Dopamine Neurons ◽

Reward Circuitry ◽

Reward Seeking ◽

Brain Reward ◽

Midbrain Dopamine ◽

The Brain ◽

Midbrain Dopamine Neurons

AbstractThe neurobiological study of reward was launched by the discovery of intracranial self-stimulation (ICSS). Subsequent investigation of this phenomenon provided the initial link between reward-seeking behavior and dopaminergic neurotransmission. We re-evaluated this relationship by psychophysical, pharmacological, optogenetic, and computational means. In rats working for direct, optical activation of midbrain dopamine neurons, we varied the strength and opportunity cost of the stimulation and measured time allocation, the proportion of trial time devoted to reward pursuit. We found that the dependence of time allocation on the strength and cost of stimulation was similar formally to that observed when electrical stimulation of the medial forebrain bundle served as the reward. When the stimulation is strong and cheap, the rats devote almost all their time to reward pursuit; time allocation falls off as stimulation strength is decreased and/or its opportunity cost is increased. A 3D plot of time allocation versus stimulation strength and cost produces a surface resembling the corner of a plateau (the “reward mountain”). We show that dopamine-transporter blockade shifts the mountain along both the strength and cost axes in rats working for optical activation of midbrain dopamine neurons. In contrast, the same drug shifted the mountain uniquely along the opportunity-cost axis when rats worked for electrical MFB stimulation in a prior study. Dopamine neurons are an obligatory stage in the dominant model of ICSS, which positions them at a key nexus in the final common path for reward seeking. This model fails to provide a cogent account for the differential effect of dopamine transporter blockade on the reward mountain. Instead, we propose that midbrain dopamine neurons and neurons with non-dopaminergic, MFB axons constitute parallel limbs of brain-reward circuitry that ultimately converge on the final-common path for the evaluation and pursuit of rewards.Author summaryTo succeed in the struggle for survival and reproductive success, animals must make wise choices about which goals to pursue and how much to pay to attain them. How does the brain make such decisions and adjust behaviour accordingly? An animal model that has long served to address this question entails delivery of rewarding brain stimulation. When the probe is positioned appropriately in the brain, rats will work indefatigably to trigger such stimulation. Dopamine neurons play a crucial role in this phenomenon. The dominant model of the brain circuitry responsible for the reward-seeking behavior treats these cells as a gateway through which the reward-generating brain signals must pass. Here, we challenge this idea on the basis of an experiment in which the dopamine neurons were activated selectively and directly. Mathematical modeling of the results argues for a new view of the structure of brain reward circuitry. On this view, the pathway(s) in which the dopamine neurons are embedded is one of a set of parallel channels that process reward signals in the brain. To achieve a full understanding of how goals are evaluated, selected and pursued, the full set of channels must be identified and investigated.

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Role of the dorsal diencephalic conduction system in the brain reward circuitry

Behavioural Brain Research ◽

10.1016/j.bbr.2015.10.038 ◽

2016 ◽

Vol 296 ◽

pp. 431-441 ◽

Cited By ~ 8

Author(s):

Marc Fakhoury ◽

Pierre-Paul Rompré ◽

Sandra M. Boye

Keyword(s):

Conduction System ◽

Reward Circuitry ◽

Brain Reward ◽

The Brain

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Anhedonia and the Brain Reward Circuitry in Depression

Current Behavioral Neuroscience Reports ◽

10.1007/s40473-015-0044-3 ◽

2015 ◽

Vol 2 (3) ◽

pp. 146-153 ◽

Cited By ~ 88

Author(s):

Mitra Heshmati ◽

Scott J. Russo

Keyword(s):

Reward Circuitry ◽

Brain Reward ◽

The Brain

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Erratum: The brain reward circuitry in mood disorders

Nature Reviews Neuroscience ◽

10.1038/nrn3589 ◽

2013 ◽

Vol 14 (10) ◽

pp. 736-736 ◽

Cited By ~ 3

Author(s):

Scott J. Russo ◽

Eric J. Nestler

Keyword(s):

Mood Disorders ◽

Reward Circuitry ◽

Brain Reward ◽

The Brain

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Obesity is associated with high serotonin 4 receptor availability in the brain reward circuitry

NeuroImage ◽

10.1016/j.neuroimage.2012.03.050 ◽

2012 ◽

Vol 61 (4) ◽

pp. 884-888 ◽

Cited By ~ 36

Author(s):

M.E. Haahr ◽

P.M. Rasmussen ◽

K. Madsen ◽

L. Marner ◽

C. Ratner ◽

...

Keyword(s):

Reward Circuitry ◽

Brain Reward ◽

The Brain

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Learning of food preferences: mechanisms and implications for obesity & metabolic diseases

International Journal of Obesity ◽

10.1038/s41366-021-00894-3 ◽

2021 ◽

Author(s):

Hans-Rudolf Berthoud ◽

Christopher D. Morrison ◽

Karen Ackroff ◽

Anthony Sclafani

Keyword(s):

Metabolic Diseases ◽

Food Preferences ◽

Reward System ◽

Nutrient Sensing ◽

Vagal Afferents ◽

Dietary Knowledge ◽

Ongoing Work ◽

Brain Reward ◽

The Brain ◽

Vagal Function

AbstractOmnivores, including rodents and humans, compose their diets from a wide variety of potential foods. Beyond the guidance of a few basic orosensory biases such as attraction to sweet and avoidance of bitter, they have limited innate dietary knowledge and must learn to prefer foods based on their flavors and postoral effects. This review focuses on postoral nutrient sensing and signaling as an essential part of the reward system that shapes preferences for the associated flavors of foods. We discuss the extensive array of sensors in the gastrointestinal system and the vagal pathways conveying information about ingested nutrients to the brain. Earlier studies of vagal contributions were limited by nonselective methods that could not easily distinguish the contributions of subsets of vagal afferents. Recent advances in technique have generated substantial new details on sugar- and fat-responsive signaling pathways. We explain methods for conditioning flavor preferences and their use in evaluating gut–brain communication. The SGLT1 intestinal sugar sensor is important in sugar conditioning; the critical sensors for fat are less certain, though GPR40 and 120 fatty acid sensors have been implicated. Ongoing work points to particular vagal pathways to brain reward areas. An implication for obesity treatment is that bariatric surgery may alter vagal function.

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