From the stomach to locus coeruleus: new neural substrate for ghrelin’s effects on ingestive, motivated and anxiety-like behaviors
Ghrelin, a stomach-derived orexigenic hormone, has a well-established role in energy homeostasis, food reward, and emotionality. Noradrenergic neurons of the locus coeruleus (LC) are known to play an important role in arousal, emotion, cognition, but recently have also been implicated in control of...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1286805/full |
| _version_ | 1827763374950187008 |
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| author | Ivana Maric Ivana Maric Lorena López-Ferreras Yashaswini Bhat Mohammed Asker Stina Börchers Stina Börchers Lauren Bellfy Lauren Bellfy Suyeun Byun Janine L. Kwapis Janine L. Kwapis Karolina P. Skibicka Karolina P. Skibicka Karolina P. Skibicka |
| author_facet | Ivana Maric Ivana Maric Lorena López-Ferreras Yashaswini Bhat Mohammed Asker Stina Börchers Stina Börchers Lauren Bellfy Lauren Bellfy Suyeun Byun Janine L. Kwapis Janine L. Kwapis Karolina P. Skibicka Karolina P. Skibicka Karolina P. Skibicka |
| author_sort | Ivana Maric |
| collection | DOAJ |
| description | Ghrelin, a stomach-derived orexigenic hormone, has a well-established role in energy homeostasis, food reward, and emotionality. Noradrenergic neurons of the locus coeruleus (LC) are known to play an important role in arousal, emotion, cognition, but recently have also been implicated in control of feeding behavior. Ghrelin receptors (the growth hormone secretagogue receptor, GHSR) may be found in the LC, but the behavioral effects of ghrelin signaling in this area are still unexplored. Here, we first determined whether GHSR are present in the rat LC, and demonstrate that GHSR are expressed on noradrenergic neurons in both sexes. We next investigated whether ghrelin controls ingestive and motivated behaviors as well as anxiety-like behavior by acting in the LC. To pursue this idea, we examined the effects of LC GHSR stimulation and blockade on food intake, operant responding for a palatable food reward and, anxiety-like behavior in the open field (OF) and acoustic startle response (ASR) tests in male and female rats. Our results demonstrate that intra-LC ghrelin administration increases chow intake and motivated behavior for sucrose in both sexes. Additionally, females, but not males, exhibited a potent anxiolytic response in the ASR. In order to determine whether activation of GHSR in the LC was necessary for feeding and anxiety behavior control, we utilized liver-expressed antimicrobial peptide 2 (LEAP2), a newly identified endogenous GHSR antagonist. LEAP2 delivered specifically into the LC was sufficient to reduce fasting-induced chow hyperphagia in both sexes, but food reward only in females. Moreover, blockade of GHSR in the LC increased anxiety-like behavior measured in the ASR test in both sexes. Taken together, these results indicate that ghrelin acts in the LC to alter ingestive, motivated and anxiety-like behaviors, with a degree of sex divergence. |
| first_indexed | 2024-03-11T10:51:19Z |
| format | Article |
| id | doaj.art-bb07edda3a484c27a7557afd7a13c86f |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-11T10:51:19Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-bb07edda3a484c27a7557afd7a13c86f2023-11-13T18:00:07ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-11-011410.3389/fphar.2023.12868051286805From the stomach to locus coeruleus: new neural substrate for ghrelin’s effects on ingestive, motivated and anxiety-like behaviorsIvana Maric0Ivana Maric1Lorena López-Ferreras2Yashaswini Bhat3Mohammed Asker4Stina Börchers5Stina Börchers6Lauren Bellfy7Lauren Bellfy8Suyeun Byun9Janine L. Kwapis10Janine L. Kwapis11Karolina P. Skibicka12Karolina P. Skibicka13Karolina P. Skibicka14Institute for Neuroscience and Physiology, University of Gothenburg, Gothenburg, SwedenDepartment of Nutritional Sciences, Pennsylvania State University, State College, PA, United StatesInstitute for Neuroscience and Physiology, University of Gothenburg, Gothenburg, SwedenDepartment of Nutritional Sciences, Pennsylvania State University, State College, PA, United StatesInstitute for Neuroscience and Physiology, University of Gothenburg, Gothenburg, SwedenInstitute for Neuroscience and Physiology, University of Gothenburg, Gothenburg, SwedenDepartment of Nutritional Sciences, Pennsylvania State University, State College, PA, United StatesDepartment of Biology, Pennsylvania State University, State College, PA, United StatesHuck Institutes of the Life Sciences, Pennsylvania State University, State College, PA, United StatesDepartment of Nutritional Sciences, Pennsylvania State University, State College, PA, United StatesDepartment of Biology, Pennsylvania State University, State College, PA, United StatesHuck Institutes of the Life Sciences, Pennsylvania State University, State College, PA, United StatesInstitute for Neuroscience and Physiology, University of Gothenburg, Gothenburg, SwedenDepartment of Nutritional Sciences, Pennsylvania State University, State College, PA, United StatesHuck Institutes of the Life Sciences, Pennsylvania State University, State College, PA, United StatesGhrelin, a stomach-derived orexigenic hormone, has a well-established role in energy homeostasis, food reward, and emotionality. Noradrenergic neurons of the locus coeruleus (LC) are known to play an important role in arousal, emotion, cognition, but recently have also been implicated in control of feeding behavior. Ghrelin receptors (the growth hormone secretagogue receptor, GHSR) may be found in the LC, but the behavioral effects of ghrelin signaling in this area are still unexplored. Here, we first determined whether GHSR are present in the rat LC, and demonstrate that GHSR are expressed on noradrenergic neurons in both sexes. We next investigated whether ghrelin controls ingestive and motivated behaviors as well as anxiety-like behavior by acting in the LC. To pursue this idea, we examined the effects of LC GHSR stimulation and blockade on food intake, operant responding for a palatable food reward and, anxiety-like behavior in the open field (OF) and acoustic startle response (ASR) tests in male and female rats. Our results demonstrate that intra-LC ghrelin administration increases chow intake and motivated behavior for sucrose in both sexes. Additionally, females, but not males, exhibited a potent anxiolytic response in the ASR. In order to determine whether activation of GHSR in the LC was necessary for feeding and anxiety behavior control, we utilized liver-expressed antimicrobial peptide 2 (LEAP2), a newly identified endogenous GHSR antagonist. LEAP2 delivered specifically into the LC was sufficient to reduce fasting-induced chow hyperphagia in both sexes, but food reward only in females. Moreover, blockade of GHSR in the LC increased anxiety-like behavior measured in the ASR test in both sexes. Taken together, these results indicate that ghrelin acts in the LC to alter ingestive, motivated and anxiety-like behaviors, with a degree of sex divergence.https://www.frontiersin.org/articles/10.3389/fphar.2023.1286805/fullghrelinhindbrainlocus coeruleus (LC)food motivationanxiety-like behaviorLEAP2 |
| spellingShingle | Ivana Maric Ivana Maric Lorena López-Ferreras Yashaswini Bhat Mohammed Asker Stina Börchers Stina Börchers Lauren Bellfy Lauren Bellfy Suyeun Byun Janine L. Kwapis Janine L. Kwapis Karolina P. Skibicka Karolina P. Skibicka Karolina P. Skibicka From the stomach to locus coeruleus: new neural substrate for ghrelin’s effects on ingestive, motivated and anxiety-like behaviors Frontiers in Pharmacology ghrelin hindbrain locus coeruleus (LC) food motivation anxiety-like behavior LEAP2 |
| title | From the stomach to locus coeruleus: new neural substrate for ghrelin’s effects on ingestive, motivated and anxiety-like behaviors |
| title_full | From the stomach to locus coeruleus: new neural substrate for ghrelin’s effects on ingestive, motivated and anxiety-like behaviors |
| title_fullStr | From the stomach to locus coeruleus: new neural substrate for ghrelin’s effects on ingestive, motivated and anxiety-like behaviors |
| title_full_unstemmed | From the stomach to locus coeruleus: new neural substrate for ghrelin’s effects on ingestive, motivated and anxiety-like behaviors |
| title_short | From the stomach to locus coeruleus: new neural substrate for ghrelin’s effects on ingestive, motivated and anxiety-like behaviors |
| title_sort | from the stomach to locus coeruleus new neural substrate for ghrelin s effects on ingestive motivated and anxiety like behaviors |
| topic | ghrelin hindbrain locus coeruleus (LC) food motivation anxiety-like behavior LEAP2 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1286805/full |
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