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

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.

scholarly journals Molecular Genetic Testing in Pain and Addiction: Facts, Fiction and Clinical Utility

2015 ◽  
Vol 2 (1) ◽  
Author(s):  
Kenneth Blum ◽  
Mary Hauser ◽  
James Fratantonio ◽  
Rajendra D. Badgaiyan
Keyword(s):  
Genetic Testing ◽  
Clinical Utility ◽  
Molecular Genetic ◽  
Deficiency Syndrome ◽  
Pain Tolerance ◽  
Addictive Behaviors ◽  
Molecular Genetic Testing ◽  
Addiction Risk ◽  
Brain Reward ◽  
The Brain

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.

scholarly journals Operant behavior to obtain palatable food modifies neuronal plasticity in the brain reward circuit

2013 ◽  
Vol 23 (2) ◽  
pp. 146-159 ◽  
Author(s):  
Thomas Guegan ◽  
Laura Cutando ◽  
Eduard Ayuso ◽  
Emanuela Santini ◽  
Gilberto Fisone ◽  
...  
Keyword(s):  
Neuronal Plasticity ◽  
Operant Behavior ◽  
Palatable Food ◽  
Brain Reward ◽  
The Brain ◽  
Reward Circuit

scholarly journals Operant behavior to obtain palatable food modifies ERK activity in the brain reward circuit

2013 ◽  
Vol 23 (3) ◽  
pp. 240-252 ◽  
Author(s):  
Thomas Guegan ◽  
Laura Cutando ◽  
Giuseppe Gangarossa ◽  
Emanuela Santini ◽  
Gilberto Fisone ◽  
...  
Keyword(s):  
Operant Behavior ◽  
Palatable Food ◽  
Brain Reward ◽  
Erk Activity ◽  
The Brain ◽  
Reward Circuit

Permeability of the microcirculation in area postrema of rat

1988 ◽  
Vol 46 ◽  
pp. 348-349
Author(s):  
Shams M. Ghoneim ◽  
Frank M. Faraci ◽  
Gary L. Baumbach
Keyword(s):  
Brain Stem ◽  
Area Postrema ◽  
Upper Body ◽  
Sprague Dawley ◽  
Sodium Cacodylate ◽  
Acute Hypertension ◽  
Sprague Dawley Rats ◽  
Ultrastructural Characteristics ◽  
The Brain ◽  
Adjacent Brain

The area postrema is a circumventricular organ in the brain stem and is one of the regions in the brain that lacks a fully functional blood-brain barrier. Recently, we found that disruption of the microcirculation during acute hypertension is greater in area postrema than in the adjacent brain stem. In contrast, hyperosmolar disruption of the microcirculation is greater in brain stem. The objective of this study was to compare ultrastructural characteristics of the microcirculation in area postrema and adjacent brain stem.We studied 5 Sprague-Dawley rats. Horseradish peroxidase was injected intravenously and allowed to circulate for 1, 5 or 15 minutes. Following perfusion of the upper body with 2.25% glutaraldehyde in 0.1 M sodium cacodylate, the brain stem was removed, embedded in agar, and chopped into 50-70 μm sections with a TC-Sorvall tissue chopper. Sections of brain stem were incubated for 1 hour in a solution of 3,3' diaminobenzidine tetrahydrochloride (0.05%) in 0.05M Tris buffer with 1% H2O2.

Alcohol intake impairs glucose counterregulation during acute insulin-induced hypoglycemia in IDDM patients. Evidence for a critical role of free fatty acids

Diabetes ◽  
1993 ◽  
Vol 42 (11) ◽  
pp. 1626-1634 ◽  
Author(s):  
A. Avogaro ◽  
P. Beltramello ◽  
L. Gnudi ◽  
A. Maran ◽  
A. Valerio ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
Alcohol Intake ◽  
Critical Role

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

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.

scholarly journals In the nose or on the tongue? Contrasting motivational effects of oral and intranasal oxytocin on arousal and reward during social processing

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Juan Kou ◽  
Chunmei Lan ◽  
Yingying Zhang ◽  
Qianqian Wang ◽  
Feng Zhou ◽  
...  
Keyword(s):  
Brain Function ◽  
Intranasal Administration ◽  
Emotional Cues ◽  
Beneficial Effects ◽  
Social Processing ◽  
Concentration Changes ◽  
Brain Reward ◽  
Male Subjects ◽  
The Brain ◽  
Potential Therapeutic Intervention

AbstractIntranasal oxytocin exerts wide-ranging effects on socioemotional behavior and is proposed as a potential therapeutic intervention in psychiatric disorders. However, following intranasal administration, oxytocin could penetrate directly into the brain or influence its activity via increased peripheral concentrations crossing the blood–brain barrier or influencing vagal projections. In the current randomized, placebo-controlled, pharmaco-imaging clinical trial we investigated effects of 24IU oral (lingual) oxytocin spray, restricting it to peripherally mediated blood-borne and vagal effects, on responses to face emotions in 80 male subjects and compared them with 138 subjects treated intranasally with 24IU. Oral, but not intranasal oxytocin administration increased both arousal ratings for faces and associated brain reward responses, the latter being partially mediated by blood concentration changes. Furthermore, while oral oxytocin increased amygdala and arousal responses to face emotions, after intranasal administration they were decreased. Thus, oxytocin can produce markedly contrasting motivational effects in relation to socioemotional cues when it influences brain function via different routes. These findings have important implications for future therapeutic use since administering oxytocin orally may be both easier and have potentially stronger beneficial effects by enhancing responses to emotional cues and increasing their associated reward.

scholarly journals Reactive Oxygen Species: Beyond Their Reactive Behavior

2021 ◽  
Vol 46 (1) ◽  
pp. 77-87
Author(s):  
Arnaud Tauffenberger ◽  
Pierre J. Magistretti
Keyword(s):  
Reactive Oxygen Species ◽  
Second Messengers ◽  
Critical Role ◽  
Complex Function ◽  
Reactive Oxygen ◽  
High Reactivity ◽  
Oxygen Species ◽  
Health And Disease ◽  
Cellular Dysfunction ◽  
The Brain

AbstractCellular homeostasis plays a critical role in how an organism will develop and age. Disruption of this fragile equilibrium is often associated with health degradation and ultimately, death. Reactive oxygen species (ROS) have been closely associated with health decline and neurological disorders, such as Alzheimer’s disease or Parkinson’s disease. ROS were first identified as by-products of the cellular activity, mainly mitochondrial respiration, and their high reactivity is linked to a disruption of macromolecules such as proteins, lipids and DNA. More recent research suggests more complex function of ROS, reaching far beyond the cellular dysfunction. ROS are active actors in most of the signaling cascades involved in cell development, proliferation and survival, constituting important second messengers. In the brain, their impact on neurons and astrocytes has been associated with synaptic plasticity and neuron survival. This review provides an overview of ROS function in cell signaling in the context of aging and degeneration in the brain and guarding the fragile balance between health and disease.

Beyond the Reward Pathway: Coding Reward Magnitude and Error in the Rat Subthalamic Nucleus

2009 ◽  
Vol 102 (4) ◽  
pp. 2526-2537 ◽  
Author(s):  
Sylvie Lardeux ◽  
Remy Pernaud ◽  
Dany Paleressompoulle ◽  
Christelle Baunez
Keyword(s):  
Subthalamic Nucleus ◽  
Firing Pattern ◽  
Sucrose Solution ◽  
Critical Role ◽  
The Other ◽  
Reward Circuitry ◽  
Reward Delivery ◽  
Reward Pathway ◽  
Subthalamic Neurons ◽  
The Brain

It was recently shown that subthalamic nucleus (STN) lesions affect motivation for food, cocaine, and alcohol, differentially, according to either the nature of the reward or the preference for it. The STN may thus code a reward according to its value. Here, we investigated how the firing of subthalamic neurons is modulated during expectation of a predicted reward between two possibilities (4 or 32% sucrose solution). The firing pattern of neurons responding to predictive cues and to reward delivery indicates that STN neurons can be divided into subpopulations responding specifically to one reward and less or giving no response to the other. In addition, some neurons (“oops” neurons) specifically encode errors as they respond only during error trials. These results reveal that the STN plays a critical role in ascertaining the value of the reward and seems to encode that value differently depending on the magnitude of the reward. These data highlight the importance of the STN in the reward circuitry of the brain.

Sign in / Sign up

Export Citation Format

Share Document