Glucagon‐Like Peptide‐1 Receptor Signaling in the Ventral Tegmental Area Reduces Alcohol Self‐Administration in Male Rats

2020 ◽  
Author(s):  
Tiarani N. Dixon ◽  
Gavan P. McNally ◽  
Zhi Yi Ong
Keyword(s):  
Ventral Tegmental Area ◽  
Male Rats ◽  
Receptor Signaling ◽  
Self Administration ◽  
Glucagon Like Peptide ◽  
Ventral Tegmental ◽  
Glucagon Like Peptide 1

scholarly journals The food intake-suppressive effects of glucagon-like peptide-1 receptor signaling in the ventral tegmental area are mediated by AMPA/kainate receptors

2013 ◽  
Vol 305 (11) ◽  
pp. E1367-E1374 ◽  
Author(s):  
Elizabeth G. Mietlicki-Baase ◽  
Pavel I. Ortinski ◽  
Laura E. Rupprecht ◽  
Diana R. Olivos ◽  
Amber L. Alhadeff ◽  
...  
Keyword(s):  
Food Intake ◽  
Ventral Tegmental Area ◽  
Dopamine Neurons ◽  
Kainate Receptors ◽  
System Control ◽  
Receptor Signaling ◽  
Palatable Food ◽  
Glucagon Like Peptide ◽  
Ventral Tegmental ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 receptor (GLP-1R) activation in the ventral tegmental area (VTA) is physiologically relevant for the control of palatable food intake. Here, we tested whether the food intake-suppressive effects of VTA GLP-1R activation are mediated by glutamatergic signaling within the VTA. Intra-VTA injections of the GLP-1R agonist exendin-4 (Ex-4) reduced palatable high-fat food intake in rats primarily by reducing meal size; these effects were mediated in part via glutamatergic AMPA/kainate but not NMDA receptor signaling. Additional behavioral data indicated that GLP-1R expressed specifically within the VTA can partially mediate the intake- and body weight-suppressive effects of systemically administered Ex-4, offering the intriguing possibility that this receptor population may be clinically relevant for food intake control. Intra-VTA Ex-4 rapidly increased tyrosine hydroxylase levels within the VTA, suggesting that GLP-1R activation modulates VTA dopaminergic signaling. Further evidence for this hypothesis was provided by electrophysiological data showing that Ex-4 increased the frequency of AMPA-mediated currents and reduced the paired/pulse ratio in VTA dopamine neurons. Together, these data provide novel mechanisms by which GLP-1R agonists in the mesolimbic reward system control for palatable food intake.

scholarly journals Glucagon-Like Peptide-1 Receptor Activation in the Ventral Tegmental Area Decreases the Reinforcing Efficacy of Cocaine

2015 ◽  
Vol 41 (7) ◽  
pp. 1917-1928 ◽  
Author(s):  
Heath D Schmidt ◽  
Elizabeth G Mietlicki-Baase ◽  
Kelsey Y Ige ◽  
John J Maurer ◽  
David J Reiner ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Receptor Activation ◽  
Reinforcing Efficacy ◽  
Glucagon Like Peptide ◽  
Ventral Tegmental ◽  
Glucagon Like Peptide 1

scholarly journals Glucagon-like peptide-1 receptor activation in the ventral tegmental area attenuates cocaine seeking in rats

2018 ◽  
Vol 43 (10) ◽  
pp. 2000-2008 ◽  
Author(s):  
Nicole S. Hernandez ◽  
Kelsey Y. Ige ◽  
Elizabeth G. Mietlicki-Baase ◽  
Gian Carlo Molina-Castro ◽  
Christopher A. Turner ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Receptor Activation ◽  
Cocaine Seeking ◽  
Glucagon Like Peptide ◽  
Ventral Tegmental ◽  
Glucagon Like Peptide 1

scholarly journals GLP-1 receptor signaling contributes to anorexigenic effect of centrally administered oxytocin in rats

2002 ◽  
Vol 283 (1) ◽  
pp. R99-R106 ◽  
Author(s):  
Linda Rinaman ◽  
Elizabeth E. Rothe
Keyword(s):  
Food Intake ◽  
Receptor Antagonist ◽  
Male Rats ◽  
Neural Systems ◽  
Neural Pathways ◽  
Receptor Signaling ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Access To Food ◽  
Anorexigenic Effect

The present study examined possible interactions between central glucagon-like peptide-1 (GLP-1) and oxytocin (OT) neural systems by determining whether blockade of GLP-1 receptors attenuates OT-induced anorexia and vice versa. Male rats were acclimated to daily 4-h food access. In the first experiment, rats were infused centrally with GLP-1 receptor antagonist or vehicle, followed by an anorexigenic dose of synthetic OT. Access to food began 20 min later. Cumulative food intake was measured every 30 min for 4 h. In the second experiment, rats were infused with OT receptor blocker or vehicle, followed by synthetic GLP-1 [(7–36) amide]. Subsequent food intake was monitored as before. The anorexigenic effect of OT was eliminated in rats pretreated with the GLP-1 receptor antagonist. Conversely, GLP-1-induced anorexia was not affected by blockade of OT receptors. In a separate immunocytochemical study, OT-positive terminals were found closely apposed to GLP-1-positive perikarya, and central infusion of OT activated c-Fos expression in GLP-1 neurons. These findings implicate endogenous GLP-1 receptor signaling as an important downstream mediator of anorexia in rats after activation of central OT neural pathways.

scholarly journals Glucagon-Like Peptide-1 (GLP-1) and 5-Hydroxytryptamine 2c (5-HT2c) Receptor Agonists in the Ventral Tegmental Area (VTA) Inhibit Ghrelin-Stimulated Appetitive Reward

2019 ◽  
Vol 20 (4) ◽  
pp. 889 ◽  
Author(s):  
Erin Howell ◽  
Hannah Baumgartner ◽  
Lia Zallar ◽  
Joaquín Selva ◽  
Liv Engel ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Receptor Agonist ◽  
Food Reinforcement ◽  
Progressive Ratio ◽  
Sprague Dawley ◽  
Operant Responding ◽  
Orexigenic Peptide ◽  
Glucagon Like Peptide ◽  
Ventral Tegmental ◽  
Glucagon Like Peptide 1

Current literature indicates that the orexigenic peptide ghrelin increases appetitive motivation via signaling in the mesolimbic reward system. Another gastric peptide, glucagon-like peptide-1 (GLP-1), and the neurotransmitter 5-hydroxytryptamine (5-HT), are both known to suppress operant responding for food by acting on key mesolimbic nuclei, including the ventral tegmental area (VTA). In order to investigate the interaction effects of ghrelin, GLP-1, and 5-HT within the VTA, we measured operant responding for sucrose pellets after the administration of ghrelin, the GLP-1 receptor agonist exendin-4 (Ex-4), and the 5-HT2c receptor agonist Ro60-0175 in male Sprague-Dawley rats. Following training on a progressive ratio 3 (PR3) schedule, animals were first injected with ghrelin into the VTA at doses of 3 to 300 pmol. In subsequent testing, separate rats were administered intraperitoneal (IP) Ex-4 (0.1–1.0 µg/kg) or VTA Ex-4 (0.01–0.1 µg) paired with 300 pmol ghrelin. In a final group of rats, the 5-HT2c agonist Ro60-0175 was injected IP (0.25–1.0 mg/kg) or into the VTA (1.5–3.0 µg), and under both conditions paired with 300 pmol ghrelin delivered into the VTA. Our results indicated that ghrelin administration increased operant responding for food reward and that this effect was attenuated by IP and VTA Ex-4 pretreatment as well as pre-administration of IP or VTA Ro60-0175. These data provide compelling evidence that mesolimbic GLP-1 and serotonergic circuitry interact with the ghrelinergic system to suppress ghrelin’s effects on the mediation of food reinforcement.

scholarly journals Adolescent Nicotine Exposure Alters GABAA Receptor Signaling in the Ventral Tegmental Area and Increases Adult Ethanol Self-Administration

Cell Reports ◽  
2018 ◽  
Vol 23 (1) ◽  
pp. 68-77 ◽  
Author(s):  
Alyse M. Thomas ◽  
Alexey Ostroumov ◽  
Blake A. Kimmey ◽  
Madison B. Taormina ◽  
William M. Holden ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Gabaa Receptor ◽  
Nicotine Exposure ◽  
Receptor Signaling ◽  
Self Administration ◽  
Ventral Tegmental

scholarly journals Cocaine induces paradigm-specific changes to the transcriptome within the ventral tegmental area

2021 ◽  
Author(s):  
Rianne R. Campbell ◽  
Siwei Chen ◽  
Joy H. Beardwood ◽  
Alberto J. López ◽  
Lilyana V. Pham ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ventral Tegmental Area ◽  
Home Cage ◽  
Expression Patterns ◽  
Energy Regulation ◽  
Biological Processes ◽  
Cocaine Exposure ◽  
Self Administration ◽  
Drug Reinforcement ◽  
Ventral Tegmental

AbstractDuring the initial stages of drug use, cocaine-induced neuroadaptations within the ventral tegmental area (VTA) are critical for drug-associated cue learning and drug reinforcement processes. These neuroadaptations occur, in part, from alterations to the transcriptome. Although cocaine-induced transcriptional mechanisms within the VTA have been examined, various regimens and paradigms have been employed to examine candidate target genes. In order to identify key genes and biological processes regulating cocaine-induced processes, we employed genome-wide RNA-sequencing to analyze transcriptional profiles within the VTA from male mice that underwent one of four commonly used paradigms: acute home cage injections of cocaine, chronic home cage injections of cocaine, cocaine-conditioning, or intravenous-self administration of cocaine. We found that cocaine alters distinct sets of VTA genes within each exposure paradigm. Using behavioral measures from cocaine self-administering mice, we also found several genes whose expression patterns corelate with cocaine intake. In addition to overall gene expression levels, we identified several predicted upstream regulators of cocaine-induced transcription shared across all paradigms. Although distinct gene sets were altered across cocaine exposure paradigms, we found, from Gene Ontology (GO) term analysis, that biological processes important for energy regulation and synaptic plasticity were affected across all cocaine paradigms. Coexpression analysis also identified gene networks that are altered by cocaine. These data indicate that cocaine alters networks enriched with glial cell markers of the VTA that are involved in gene regulation and synaptic processes. Our analyses demonstrate that transcriptional changes within the VTA depend on the route, dose and context of cocaine exposure, and highlight several biological processes affected by cocaine. Overall, these findings provide a unique resource of gene expression data for future studies examining novel cocaine gene targets that regulate drug-associated behaviors.

scholarly journals Inflammatory Pain Promotes Increased Opioid Self-Administration: Role of Dysregulated Ventral Tegmental Area   Opioid Receptors

2015 ◽  
Vol 35 (35) ◽  
pp. 12217-12231 ◽  
Author(s):  
L. Hipolito ◽  
A. Wilson-Poe ◽  
Y. Campos-Jurado ◽  
E. Zhong ◽  
J. Gonzalez-Romero ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Opioid Receptors ◽  
Inflammatory Pain ◽  
Self Administration ◽  
Ventral Tegmental
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