GHSR blockade, but not reduction of peripherally circulating ghrelin via β
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
05 Sep 2024
05 Sep 2024
Historique:
received:
20
10
2023
accepted:
21
08
2024
revised:
17
08
2024
medline:
5
9
2024
pubmed:
5
9
2024
entrez:
4
9
2024
Statut:
aheadofprint
Résumé
Alcohol use disorder (AUD) and binge drinking are highly prevalent public health issues. The stomach-derived peptide ghrelin, and its receptor, the growth hormone secretagogue receptor (GHSR), both of which are expressed in the brain and periphery, are implicated in alcohol-related outcomes. We previously found that systemic and central administration of GHSR antagonists reduced binge-like alcohol drinking, whereas a ghrelin vaccine did not. Thus, we hypothesized that central GHSR drives binge-like alcohol drinking independently of peripheral ghrelin. To investigate this hypothesis, we antagonized β
Identifiants
pubmed: 39232198
doi: 10.1038/s41380-024-02713-3
pii: 10.1038/s41380-024-02713-3
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
Références
Understanding binge drinking. https://www.niaaa.nih.gov/publications/brochures-and-fact-sheets/binge-drinking , Accessed Date Accessed.
Morley KC, Perry CJ, Watt J, Hurzeler T, Leggio L, Lawrence AJ, et al. New approved and emerging pharmacological approaches to alcohol use disorder: a review of clinical studies. Expert Opin Pharmacother. 2021;22:1291–303.
pubmed: 33615945
doi: 10.1080/14656566.2021.1892641
Deschaine SL, Farokhnia M, Gregory-Flores A, Zallar LJ, You ZB, Sun H, et al. A closer look at alcohol-induced changes in the ghrelin system: novel insights from preclinical and clinical data. Addict Biol. 2022;27:e13033.
pubmed: 33908131
doi: 10.1111/adb.13033
Dass NB, Munonyara M, Bassil AK, Hervieu GJ, Osbourne S, Corcoran S, et al. Growth hormone secretagogue receptors in rat and human gastrointestinal tract and the effects of ghrelin. Neuroscience. 2003;120:443–53.
pubmed: 12890514
doi: 10.1016/S0306-4522(03)00327-0
Guan XM, Yu H, Palyha OC, McKee KK, Feighner SD, Sirinathsinghji DJ, et al. Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues. Brain Res Mol Brain Res. 1997;48:23–29.
pubmed: 9379845
doi: 10.1016/S0169-328X(97)00071-5
Ge XC, Yang H, Bednarek MA, Galon-Tilleman H, Chen PR, Chen M, et al. LEAP2 is an endogenous antagonist of the ghrelin receptor. Cell Metab. 2018;27:461-+.
pubmed: 29233536
doi: 10.1016/j.cmet.2017.10.016
Farokhnia M, Faulkner ML, Piacentino D, Lee MR, Leggio L. Ghrelin: from a gut hormone to a potential therapeutic target for alcohol use disorder. Physiol Behav. 2019;204:49–57.
pubmed: 30738971
doi: 10.1016/j.physbeh.2019.02.008
Jerlhag E. Animal studies reveal that the ghrelin pathway regulates alcohol-mediated responses. Front Psychiatry. 2023;14:1050973.
pubmed: 36970276
pmcid: 10030715
doi: 10.3389/fpsyt.2023.1050973
Leggio L, Ferrulli A, Cardone S, Nesci A, Miceli A, Malandrino N, et al. Ghrelin system in alcohol-dependent subjects: role of plasma ghrelin levels in alcohol drinking and craving. Addict Biol. 2012;17:452–64.
pubmed: 21392177
doi: 10.1111/j.1369-1600.2010.00308.x
Leggio L, Zywiak WH, Fricchione SR, Edwards SM, de la Monte SM, Swift RM, et al. Intravenous ghrelin administration increases alcohol craving in alcohol-dependent heavy drinkers: a preliminary investigation. Biol Psychiatry. 2014;76:734–41.
pubmed: 24775991
pmcid: 4176606
doi: 10.1016/j.biopsych.2014.03.019
Farokhnia M, Grodin EN, Lee MR, Oot EN, Blackburn AN, Stangl BL, et al. Exogenous ghrelin administration increases alcohol self-administration and modulates brain functional activity in heavy-drinking alcohol-dependent individuals. Mol Psychiatry. 2018;23:2029–38.
pubmed: 29133954
doi: 10.1038/mp.2017.226
Jerlhag E, Egecioglu E, Landgren S, Salome N, Heilig M, Moechars D, et al. Requirement of central ghrelin signaling for alcohol reward. Proc Natl Acad Sci USA. 2009;106:11318–23.
pubmed: 19564604
pmcid: 2703665
doi: 10.1073/pnas.0812809106
Jerlhag E. Systemic administration of ghrelin induces conditioned place preference and stimulates accumbal dopamine. Addict Biol. 2008;13:358–63.
pubmed: 18782383
doi: 10.1111/j.1369-1600.2008.00125.x
Jerlhag E, Landgren S, Egecioglu E, Dickson SL, Engel JA. The alcohol-induced locomotor stimulation and accumbal dopamine release is suppressed in ghrelin knockout mice. Alcohol. 2011;45:341–7.
pubmed: 21145690
doi: 10.1016/j.alcohol.2010.10.002
Kaur S, Ryabinin AE. Ghrelin receptor antagonism decreases alcohol consumption and activation of perioculomotor urocortin-containing neurons. Alcohol Clin Exp Res. 2010;34:1525–34.
pubmed: 20586761
pmcid: 2929279
doi: 10.1111/j.1530-0277.2010.01237.x
Gomez JL, Cunningham CL, Finn DA, Young EA, Helpenstell LK, Schuette LM, et al. Differential effects of ghrelin antagonists on alcohol drinking and reinforcement in mouse and rat models of alcohol dependence. Neuropharmacology. 2015;97:182–93.
pubmed: 26051399
pmcid: 4537402
doi: 10.1016/j.neuropharm.2015.05.026
Gomez JL, Ryabinin AE. The effects of ghrelin antagonists [D-Lys(3)]-GHRP-6 or JMV2959 on ethanol, water, and food intake in C57BL/6J mice. Alcohol Clin Exp Res. 2014;38:2436–44.
pubmed: 25257292
pmcid: 4179906
doi: 10.1111/acer.12499
Landgren S, Simms JA, Hyytia P, Engel JA, Bartlett SE, Jerlhag E. Ghrelin receptor (GHS-R1A) antagonism suppresses both operant alcohol self-administration and high alcohol consumption in rats. Addict Biol. 2012;17:86–94.
pubmed: 21309944
doi: 10.1111/j.1369-1600.2010.00280.x
Zallar LJ, Beurmann S, Tunstall BJ, Fraser CM, Koob GF, Vendruscolo LF, et al. Ghrelin receptor deletion reduces binge-like alcohol drinking in rats. J Neuroendocrinol. 2019;31:e12663.
pubmed: 30456835
doi: 10.1111/jne.12663
Bahi A, Tolle V, Fehrentz JA, Brunel L, Martinez J, Tomasetto CL, et al. Ghrelin knockout mice show decreased voluntary alcohol consumption and reduced ethanol-induced conditioned place preference. Peptides. 2013;43:48–55.
pubmed: 23428971
doi: 10.1016/j.peptides.2013.02.008
Suchankova P, Steensland P, Fredriksson I, Engel JA, Jerlhag E. Ghrelin receptor (GHS-R1A) antagonism suppresses both alcohol consumption and the alcohol deprivation effect in rats following long-term voluntary alcohol consumption. PLoS One. 2013;8:e71284.
pubmed: 23977009
pmcid: 3748070
doi: 10.1371/journal.pone.0071284
Suchankova P, Engel JA, Jerlhag E. Sub-chronic ghrelin receptor blockade attenuates alcohol- and amphetamine-induced locomotor stimulation in mice. Alcohol Alcohol. 2016;51:121–7.
pubmed: 26330568
doi: 10.1093/alcalc/agv100
Stevenson JR, Buirkle JM, Buckley LE, Young KA, Albertini KM, Bohidar AE. GHS-R1A antagonism reduces alcohol but not sucrose preference in prairie voles. Physiol Behav. 2015;147:23–29.
pubmed: 25843741
doi: 10.1016/j.physbeh.2015.04.001
Stevenson JR, Francomacaro LM, Bohidar AE, Young KA, Pesarchick BF, Buirkle JM, et al. Ghrelin receptor (GHS-R1A) antagonism alters preference for ethanol and sucrose in a concentration-dependent manner in prairie voles. Physiol Behav. 2016;155:231–6.
pubmed: 26723269
doi: 10.1016/j.physbeh.2015.12.017
Davis JF, Schurdak JD, Magrisso IJ, Mul JD, Grayson BE, Pfluger PT, et al. Gastric bypass surgery attenuates ethanol consumption in ethanol-preferring rats. Biol Psychiatry. 2012;72:354–60.
pubmed: 22444202
doi: 10.1016/j.biopsych.2012.01.035
Richardson RS, Sulima A, Rice KC, Kucharczk JA, Janda KD, Nisbett KE, et al. Pharmacological GHSR (ghrelin receptor) blockade reduces alcohol binge-like drinking in male and female mice. Neuropharmacology. 2023;238:109643.
pubmed: 37369277
doi: 10.1016/j.neuropharm.2023.109643
Hedegaard MA, Holst B. The complex signaling pathways of the ghrelin receptor. Endocrinology. 2020;161:bqaa020.
pubmed: 32049280
doi: 10.1210/endocr/bqaa020
Yanagi S, Sato T, Kangawa K, Nakazato M. The homeostatic force of ghrelin. Cell Metab. 2018;27:786–804.
pubmed: 29576534
doi: 10.1016/j.cmet.2018.02.008
Jerlhag E, Ivanoff L, Vater A, Engel JA. Peripherally circulating ghrelin does not mediate alcohol-induced reward and alcohol intake in rodents. Alcohol Clin Exp Res. 2014;38:959–68.
pubmed: 24428428
pmcid: 4112802
doi: 10.1111/acer.12337
Shearman LP, Wang SP, Helmling S, Stribling DS, Mazur P, Ge L, et al. Ghrelin neutralization by a ribonucleic acid-SPM ameliorates obesity in diet-induced obese mice. Endocrinology. 2006;147:1517–26.
pubmed: 16339202
doi: 10.1210/en.2005-0993
Kobelt P, Helmling S, Stengel A, Wlotzka B, Andresen V, Klapp BF, et al. Anti-ghrelin Spiegelmer NOX-B11 inhibits neurostimulatory and orexigenic effects of peripheral ghrelin in rats. Gut. 2006;55:788–92.
pubmed: 15994217
pmcid: 1856241
doi: 10.1136/gut.2004.061010
Wenthur CJ, Gautam R, Zhou B, Vendruscolo LF, Leggio L, Janda KD. Ghrelin receptor influence on cocaine reward is not directly dependent on peripheral acyl-ghrelin. Sci Rep. 2019;9:1841.
pubmed: 30755699
pmcid: 6372697
doi: 10.1038/s41598-019-38549-z
Perello M, Sakata I, Birnbaum S, Chuang JC, Osborne-Lawrence S, Rovinsky SA, et al. Ghrelin increases the rewarding value of high-fat diet in an orexin-dependent manner. Biol Psychiatry. 2010;67:880–6.
pubmed: 20034618
doi: 10.1016/j.biopsych.2009.10.030
Skibicka KP, Shirazi RH, Rabasa-Papio C, Alvarez-Crespo M, Neuber C, Vogel H, et al. Divergent circuitry underlying food reward and intake effects of ghrelin: dopaminergic VTA-accumbens projection mediates ghrelin’s effect on food reward but not food intake. Neuropharmacology. 2013;73:274–83.
pubmed: 23770258
doi: 10.1016/j.neuropharm.2013.06.004
Zhao TJ, Sakata I, Li RL, Liang G, Richardson JA, Brown MS, et al. Ghrelin secretion stimulated by beta1-adrenergic receptors in cultured ghrelinoma cells and in fasted mice. Proc Natl Acad Sci USA. 2010;107:15868–73.
pubmed: 20713709
pmcid: 2936616
doi: 10.1073/pnas.1011116107
Gagnon J, Anini Y. Insulin and norepinephrine regulate ghrelin secretion from a rat primary stomach cell culture. Endocrinology. 2012;153:3646–56.
pubmed: 22691550
doi: 10.1210/en.2012-1040
Goldstein JL, Zhao TJ, Li RL, Sherbet DP, Liang G, Brown MS. Surviving starvation: essential role of the ghrelin-growth hormone axis. Cold Spring Harb Symp Quant Biol. 2011;76:121–7.
pubmed: 21785007
doi: 10.1101/sqb.2011.76.010447
Gupta D, Chuang JC, Mani BK, Shankar K, Rodriguez JA, Osborne-Lawrence S, et al. beta1-adrenergic receptors mediate plasma acyl-ghrelin elevation and depressive-like behavior induced by chronic psychosocial stress. Neuropsychopharmacology. 2019;44:1319–27.
pubmed: 30758330
pmcid: 6785135
doi: 10.1038/s41386-019-0334-7
Mani BK, Osborne-Lawrence S, Vijayaraghavan P, Hepler C, Zigman JM. beta1-Adrenergic receptor deficiency in ghrelin-expressing cells causes hypoglycemia in susceptible individuals. J Clin Invest. 2016;126:3467–78.
pubmed: 27548523
pmcid: 5004971
doi: 10.1172/JCI86270
Koyama H, Iwakura H, Dote K, Bando M, Hosoda H, Ariyasu H, et al. Comprehensive Profiling of GPCR Expression in Ghrelin-Producing Cells. Endocrinology. 2016;157:692–704.
pubmed: 26671185
doi: 10.1210/en.2015-1784
You ZB, Galaj E, Alen F, Wang B, Bi GH, Moore AR, et al. Involvement of the ghrelin system in the maintenance and reinstatement of cocaine-motivated behaviors: a role of adrenergic action at peripheral beta1 receptors. Neuropsychopharmacology. 2022;47:1449–60.
pubmed: 34923576
doi: 10.1038/s41386-021-01249-2
Harris GC, Hedaya MA, Pan WJ, Kalivas P. beta-adrenergic antagonism alters the behavioral and neurochemical responses to cocaine. Neuropsychopharmacology. 1996;14:195–204.
pubmed: 8866703
doi: 10.1016/0893-133X(95)00089-V
Merritt CR, Garcia EJ, Brehm VD, Fox RG, Moeller FG, Anastasio NC, et al. Ghrelin receptor antagonist JMV2959 blunts cocaine and oxycodone drug-seeking, but not self-administration, in male rats. Front Pharmacol. 2023;14:1268366.
pubmed: 37795028
pmcid: 10545966
doi: 10.3389/fphar.2023.1268366
Fredriksson I, Jayaram-Lindstrom N, Wirf M, Nylander E, Nystrom E, Jardemark K, et al. Evaluation of guanfacine as a potential medication for alcohol use disorder in long-term drinking rats: behavioral and electrophysiological findings. Neuropsychopharmacology. 2015;40:1130–40.
pubmed: 25359257
doi: 10.1038/npp.2014.294
Froehlich JC, Hausauer B, Fischer S, Wise B, Rasmussen DD. Prazosin reduces alcohol intake in an animal model of alcohol relapse. Alcohol Clin Exp Res. 2015;39:1538–46.
pubmed: 26207767
pmcid: 4515780
doi: 10.1111/acer.12789
Gilpin NW, Koob GF. Effects of beta-adrenoceptor antagonists on alcohol drinking by alcohol-dependent rats. Psychopharmacology (Berl). 2010;212:431–9.
pubmed: 20676608
doi: 10.1007/s00213-010-1967-8
Lopez MF, Reasons SE, Carper BA, Nolen TL, Williams RL, Becker HC. Evaluation of the effect of doxasozin and zonisamide on voluntary ethanol intake in mice that experienced chronic intermittent ethanol exposure and stress. Alcohol. 2020;89:37–42.
pubmed: 32712186
pmcid: 7719616
doi: 10.1016/j.alcohol.2020.07.005
O’Neil ML, Beckwith LE, Kincaid CL, Rasmussen DD. The alpha1-adrenergic receptor antagonist, doxazosin, reduces alcohol drinking in alcohol-preferring (P) Rats. Alcohol Clin Exp Res. 2013;37:202–12.
pubmed: 22758213
doi: 10.1111/j.1530-0277.2012.01884.x
Rasmussen DD, Alexander L, Malone J, Federoff D, Froehlich JC. The alpha2-adrenergic receptor agonist, clonidine, reduces alcohol drinking in alcohol-preferring (P) rats. Alcohol. 2014;48:543–9.
pubmed: 25085719
pmcid: 4163132
doi: 10.1016/j.alcohol.2014.07.002
Rasmussen DD, Alexander LL, Raskind MA, Froehlich JC. The alpha1-adrenergic receptor antagonist, prazosin, reduces alcohol drinking in alcohol-preferring (P) rats. Alcohol Clin Exp Res. 2009;33:264–72.
pubmed: 19032582
doi: 10.1111/j.1530-0277.2008.00829.x
Rasmussen DD, Beckwith LE, Kincaid CL, Froehlich JC. Combining the alpha1 -adrenergic receptor antagonist, prazosin, with the beta-adrenergic receptor antagonist, propranolol, reduces alcohol drinking more effectively than either drug alone. Alcohol Clin Exp Res. 2014;38:1532–9.
pubmed: 24891220
pmcid: 4047654
doi: 10.1111/acer.12441
Walker BM, Rasmussen DD, Raskind MA, Koob GF. alpha1-noradrenergic receptor antagonism blocks dependence-induced increases in responding for ethanol. Alcohol. 2008;42:91–97.
pubmed: 18358987
pmcid: 2587143
doi: 10.1016/j.alcohol.2007.12.002
Froehlich JC, Hausauer BJ, Federoff DL, Fischer SM, Rasmussen DD. Prazosin reduces alcohol drinking throughout prolonged treatment and blocks the initiation of drinking in rats selectively bred for high alcohol intake. Alcohol Clin Exp Res. 2013;37:1552–60.
pubmed: 23731093
pmcid: 3775948
doi: 10.1111/acer.12116
Froehlich JC, Hausauer BJ, Rasmussen DD. Combining naltrexone and prazosin in a single oral medication decreases alcohol drinking more effectively than does either drug alone. Alcohol Clin Exp Res. 2013;37:1763–70.
pubmed: 23875623
pmcid: 3795831
doi: 10.1111/acer.12148
De Oliveira Sergio T, Wean S, Katner SN, Hopf FW. The role of beta- and alpha-adrenergic receptors on alcohol drinking. Neuropharmacology. 2023;234:109545.
pubmed: 37100382
pmcid: 11071639
doi: 10.1016/j.neuropharm.2023.109545
Le AD, Harding S, Juzytsch W, Funk D, Shaham Y. Role of alpha-2 adrenoceptors in stress-induced reinstatement of alcohol seeking and alcohol self-administration in rats. Psychopharmacology (Berl). 2005;179:366–73.
pubmed: 15551068
doi: 10.1007/s00213-004-2036-y
Skelly MJ, Weiner JL. Chronic treatment with prazosin or duloxetine lessens concurrent anxiety-like behavior and alcohol intake: evidence of disrupted noradrenergic signaling in anxiety-related alcohol use. Brain Behav. 2014;4:468–83.
pubmed: 25161814
pmcid: 4128029
doi: 10.1002/brb3.230
Varodayan FP, Patel RR, Matzeu A, Wolfe SA, Curley DE, Khom S, et al. The Amygdala Noradrenergic System Is Compromised With Alcohol Use Disorder. Biol Psychiatry. 2022;91:1008–18.
pubmed: 35430085
pmcid: 9167785
doi: 10.1016/j.biopsych.2022.02.006
Chesworth R, Corbit LH. Noradrenergic beta-receptor antagonism in the basolateral amygdala impairs reconsolidation, but not extinction, of alcohol self-administration: Intra-BLA propranolol impairs reconsolidation of alcohol self-administration. Neurobiol Learn Mem. 2018;151:59–70.
pubmed: 29649583
doi: 10.1016/j.nlm.2018.04.009
Burnham NW, Chaimowitz CN, Vis CC, Segantine Dornellas AP, Navarro M, Thiele TE. Lateral hypothalamus-projecting noradrenergic locus coeruleus pathway modulates binge-like ethanol drinking in male and female TH-ires-cre mice. Neuropharmacology. 2021;196:108702.
pubmed: 34246685
pmcid: 8434995
doi: 10.1016/j.neuropharm.2021.108702
Hassan H, Greco LV, Meshoyrer DI, Li Y, Zhang Y, Cohen TJ. Novel beta-blocker pretreatment prevents alcohol-induced atrial fibrillation in a rat model. Heart Rhythm O2. 2020;1:120–5.
pubmed: 34113866
pmcid: 8183851
doi: 10.1016/j.hroo.2020.02.006
Nicol M, Sadoune M, Polidano E, Launay JM, Samuel JL, Azibani F, et al. Doxorubicin-induced and trastuzumab-induced cardiotoxicity in mice is not prevented by metoprolol. ESC Heart Fail. 2021;8:928–37.
pubmed: 33529501
pmcid: 8006653
doi: 10.1002/ehf2.13198
Rezkalla S, Kloner RA, Khatib G, Smith FE, Khatib R. Effect of metoprolol in acute coxsackievirus B3 murine myocarditis. J Am Coll Cardiol. 1988;12:412–4.
pubmed: 2839568
doi: 10.1016/0735-1097(88)90414-7
Tran T, Mach J, Gemikonakli G, Wu H, Allore H, Howlett SE, et al. Diurnal effects of polypharmacy with high drug burden index on physical activities over 23 h differ with age and sex. Sci Rep. 2022;12:2168.
pubmed: 35140291
pmcid: 8828819
doi: 10.1038/s41598-022-06039-4
Hefnawy MM, Al-Shehri MM, Abounassif MA, Mostafa GA. Enantioselective quantification of atenolol in mouse plasma by high performance liquid chromatography using a chiral Stationary phase: application to a pharmacokinetic study. J AOAC Int. 2013;96:976–80.
pubmed: 24282934
doi: 10.5740/jaoacint.11-191
Lee MR, Tapocik JD, Ghareeb M, Schwandt ML, Dias AA, Le AN, et al. The novel ghrelin receptor inverse agonist PF-5190457 administered with alcohol: preclinical safety experiments and a phase 1b human laboratory study. Mol Psychiatry. 2020;25:461–75.
pubmed: 29728704
doi: 10.1038/s41380-018-0064-y
Chuong V, Farokhnia M, Khom S, Pince CL, Elvig SK, Vlkolinsky R, et al. The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission. JCI Insight. 2023;8:e170671.
pubmed: 37192005
pmcid: 10371247
doi: 10.1172/jci.insight.170671
Farokhnia M, Rentsch CT, Chuong V, McGinn MA, Elvig SK, Douglass EA, et al. Spironolactone as a potential new pharmacotherapy for alcohol use disorder: convergent evidence from rodent and human studies. Mol Psychiatry. 2022;27:4642–52.
pubmed: 36123420
pmcid: 10231646
doi: 10.1038/s41380-022-01736-y
Rhodes JS, Best K, Belknap JK, Finn DA, Crabbe JC. Evaluation of a simple model of ethanol drinking to intoxication in C57BL/6J mice. Physiol Behav. 2005;84:53–63.
pubmed: 15642607
doi: 10.1016/j.physbeh.2004.10.007
Thiele TE, Crabbe JC, Boehm SL 2nd. “Drinking in the Dark” (DID): a simple mouse model of binge-like alcohol intake. Curr Protoc Neurosci. 2014;68:9 49 41–12.
doi: 10.1002/0471142301.ns0949s68
Mani BK, Puzziferri N, He Z, Rodriguez JA, Osborne-Lawrence S, Metzger NP, et al. LEAP2 changes with body mass and food intake in humans and mice. J Clin Invest. 2019;129:3909–23.
pubmed: 31424424
pmcid: 6715358
doi: 10.1172/JCI125332
Deschaine SL, Leggio L. From “Hunger Hormone” to “It’s Complicated”: ghrelin beyond feeding control. Physiology (Bethesda). 2022;37:5–15.
pubmed: 34964687
Fernandez G, Cabral A, Cornejo MP, De Francesco PN, Garcia-Romero G, Reynaldo M, et al. Des-acyl ghrelin directly targets the arcuate nucleus in a ghrelin-receptor independent manner and impairs the orexigenic effect of ghrelin. J Neuroendocrinol. 2016;28:12349.
pubmed: 26661382
doi: 10.1111/jne.12349
Iwakura H, Ensho T, Ueda Y. Desacyl-ghrelin, not just an inactive form of ghrelin? A review of current knowledge on the biological actions of desacyl-ghrelin. Peptides. 2023;167:171050.
pubmed: 37392995
doi: 10.1016/j.peptides.2023.171050
Callaghan B, Furness JB. Novel and conventional receptors for ghrelin, desacyl-ghrelin, and pharmacologically related compounds. Pharmacol Rev. 2014;66:984–1001.
pubmed: 25107984
doi: 10.1124/pr.113.008433
Cabral A, Lopez Soto EJ, Epelbaum J, Perello M. Is ghrelin synthesized in the central nervous system? Int J Mol Sci. 2017;18:638.
pubmed: 28294994
pmcid: 5372651
doi: 10.3390/ijms18030638
Perello M, Cabral A, Cornejo MP, De Francesco PN, Fernandez G, Uriarte M. Brain accessibility delineates the central effects of circulating ghrelin. J Neuroendocrinol. 2019;31:e12677.
pubmed: 30582239
doi: 10.1111/jne.12677
Uriarte M, De Francesco PN, Fernandez G, Cabral A, Castrogiovanni D, Lalonde T, et al. Evidence supporting a role for the blood-cerebrospinal fluid barrier transporting circulating ghrelin into the brain. Mol Neurobiol. 2019;56:4120–34.
pubmed: 30276663
doi: 10.1007/s12035-018-1362-8
Cabral A, Fernandez G, Perello M. Analysis of brain nuclei accessible to ghrelin present in the cerebrospinal fluid. Neuroscience. 2013;253:406–15.
pubmed: 24042041
doi: 10.1016/j.neuroscience.2013.09.008
Fry M, Hoyda TD, Ferguson AV. Making sense of it: roles of the sensory circumventricular organs in feeding and regulation of energy homeostasis. Exp Biol Med (Maywood). 2007;232:14–26.
pubmed: 17202582
Wellman M, Abizaid A. Growth hormone secretagogue receptor dimers: a new pharmacological target. eNeuro. 2015;2:ENEURO.0053–14.201.
pubmed: 26464979
doi: 10.1523/ENEURO.0053-14.2015
Sustkova-Fiserova M, Jerabek P, Havlickova T, Kacer P, Krsiak M. Ghrelin receptor antagonism of morphine-induced accumbens dopamine release and behavioral stimulation in rats. Psychopharmacology (Berl). 2014;231:2899–908.
pubmed: 24531567
doi: 10.1007/s00213-014-3466-9
Zhao J, Du X, Chen M, Zhu S. Growth hormone secretagogue receptor 1A antagonist JMV2959 effectively prevents morphine memory reconsolidation and relapse. Front Pharmacol. 2021;12:718615.
pubmed: 34912212
pmcid: 8666548
doi: 10.3389/fphar.2021.718615
Wellman PJ, Clifford PS, Rodriguez J, Hughes S, Eitan S, Brunel L, et al. Pharmacologic antagonism of ghrelin receptors attenuates development of nicotine induced locomotor sensitization in rats. Regul Pept. 2011;172:77–80.
pubmed: 21903141
pmcid: 3197247
doi: 10.1016/j.regpep.2011.08.014
Jerabek P, Havlickova T, Puskina N, Charalambous C, Lapka M, Kacer P, et al. Ghrelin receptor antagonism of morphine-induced conditioned place preference and behavioral and accumbens dopaminergic sensitization in rats. Neurochem Int. 2017;110:101–13.
pubmed: 28958601
doi: 10.1016/j.neuint.2017.09.013
Clifford PS, Rodriguez J, Schul D, Hughes S, Kniffin T, Hart N, et al. Attenuation of cocaine-induced locomotor sensitization in rats sustaining genetic or pharmacologic antagonism of ghrelin receptors. Addict Biol. 2012;17:956–63.
pubmed: 21790898
doi: 10.1111/j.1369-1600.2011.00339.x
Chen YW, Barson JR, Chen A, Hoebel BG, Leibowitz SF. Opioids in the perifornical lateral hypothalamus suppress ethanol drinking. Alcohol. 2013;47:31–38.
pubmed: 23199698
doi: 10.1016/j.alcohol.2012.11.001
Chen YW, Morganstern I, Barson JR, Hoebel BG, Leibowitz SF. Differential role of D1 and D2 receptors in the perifornical lateral hypothalamus in controlling ethanol drinking and food intake: possible interaction with local orexin neurons. Alcohol Clin Exp Res. 2014;38:777–86.
pubmed: 24236888
doi: 10.1111/acer.12313
Navarro M, Olney JJ, Burnham NW, Mazzone CM, Lowery-Gionta EG, Pleil KE, et al. Lateral hypothalamus GABAergic neurons modulate consummatory behaviors regardless of the caloric content or biological relevance of the consumed stimuli. Neuropsychopharmacology. 2016;41:1505–12.
pubmed: 26442599
doi: 10.1038/npp.2015.304
Sprow GM, Rinker JA, Lowery-Gointa EG, Sparrow AM, Navarro M, Thiele TE. Lateral hypothalamic melanocortin receptor signaling modulates binge-like ethanol drinking in C57BL/6J mice. Addict Biol. 2016;21:835–46.
pubmed: 25975524
doi: 10.1111/adb.12264
Wayner MJ, Greenberg I, Carey RJ, Nolley D. Ethanol drinking elicited during electrical stimulation of the lateral hypothalamus. Physiol Behav. 1971;7:793–5.
pubmed: 5164371
doi: 10.1016/0031-9384(71)90152-1
Marchant NJ, Hamlin AS, McNally GP. Lateral hypothalamus is required for context-induced reinstatement of extinguished reward seeking. J Neurosci. 2009;29:1331–42.
pubmed: 19193880
pmcid: 6666089
doi: 10.1523/JNEUROSCI.5194-08.2009
Marchant NJ, Rabei R, Kaganovsky K, Caprioli D, Bossert JM, Bonci A, et al. A critical role of lateral hypothalamus in context-induced relapse to alcohol seeking after punishment-imposed abstinence. J Neurosci. 2014;34:7447–57.
pubmed: 24872550
pmcid: 4035512
doi: 10.1523/JNEUROSCI.0256-14.2014
Leibowitz SF, Jhanwar-Uniyal M, Dvorkin B, Makman MH. Distribution of alpha-adrenergic, beta-adrenergic and dopaminergic receptors in discrete hypothalamic areas of rat. Brain Res. 1982;233:97–114.
pubmed: 6277425
doi: 10.1016/0006-8993(82)90933-7
Leibowitz SF, Rossakis C. Pharmacological characterization of perifornical hypothalamic beta-adrenergic receptors mediating feeding inhibition in the rat. Neuropharmacology. 1978;17:691–702.
pubmed: 29257
doi: 10.1016/0028-3908(78)90082-5
Leibowitz SF. Hypothalamic alpha- and beta-adrenergic systems regulate both thirst and hunger in the rat. Proc Natl Acad Sci USA. 1971;68:332–4.
pubmed: 4395878
pmcid: 388930
doi: 10.1073/pnas.68.2.332
Leibowitz SF. Ingestion in the satiated rat: role of alpha and beta receptors in mediating effects of hypothalamic adrenergic stimulation. Physiol Behav. 1975;14:743–54.
pubmed: 1187830
doi: 10.1016/0031-9384(75)90066-9
Leibowitz SF. Paraventricular nucleus: a primary site mediating adrenergic stimulation of feeding and drinking. Pharmacol Biochem Behav. 1978;8:163–75.
pubmed: 652826
doi: 10.1016/0091-3057(78)90333-7
Leibowitz SF. Pattern of drinking and feeding produced by hypothalamic norepinephrine injection in the satiated rat. Physiol Behav. 1975;14:731–42.
pubmed: 1187829
doi: 10.1016/0031-9384(75)90065-7
Leibowitz SF. Reciprocal hunger-regulating circuits involving alpha- and beta-adrenergic receptors located, respectively, in the ventromedial and lateral hypothalamus. Proc Natl Acad Sci USA. 1970;67:1063–70.
pubmed: 4399738
pmcid: 283313
doi: 10.1073/pnas.67.2.1063
Schneider ER, Rada P, Darby RD, Leibowitz SF, Hoebel BG. Orexigenic peptides and alcohol intake: differential effects of orexin, galanin, and ghrelin. Alcohol Clin Exp Res. 2007;31:1858–65.
pubmed: 17850217
doi: 10.1111/j.1530-0277.2007.00510.x
Selvage D. Roles of the locus coeruleus and adrenergic receptors in brain-mediated hypothalamic-pituitary-adrenal axis responses to intracerebroventricular alcohol. Alcohol Clin Exp Res. 2012;36:1084–90.
pubmed: 22236039
doi: 10.1111/j.1530-0277.2011.01707.x
Burnham NW, Thiele TE. Voluntary binge-like ethanol consumption site-specifically increases c-fos immunoexpression in male C57BL6/J mice. Neuroscience. 2017;367:159–68.
pubmed: 29111360
doi: 10.1016/j.neuroscience.2017.10.027
Spencer SJ, Emmerzaal TL, Kozicz T, Andrews ZB. Ghrelin’s role in the hypothalamic-pituitary-adrenal axis stress response: implications for mood disorders. Biol Psychiatry. 2015;78:19–27.
pubmed: 25534754
doi: 10.1016/j.biopsych.2014.10.021
Chuang JC, Perello M, Sakata I, Osborne-Lawrence S, Savitt JM, Lutter M, et al. Ghrelin mediates stress-induced food-reward behavior in mice. J Clin Invest. 2011;121:2684–92.
pubmed: 21701068
pmcid: 3223843
doi: 10.1172/JCI57660
Spencer SJ, Xu L, Clarke MA, Lemus M, Reichenbach A, Geenen B, et al. Ghrelin regulates the hypothalamic-pituitary-adrenal axis and restricts anxiety after acute stress. Biol Psychiatry. 2012;72:457–65.
pubmed: 22521145
doi: 10.1016/j.biopsych.2012.03.010
Cabral A, Portiansky E, Sánchez-Jaramillo E, Zigman JM, Perello M. Ghrelin activates hypophysiotropic corticotropin-releasing factor neurons independently of the arcuate nucleus. Psychoneuroendocrinology. 2016;67:27–39.
pubmed: 26874559
pmcid: 4808343
doi: 10.1016/j.psyneuen.2016.01.027
Cabral A, De Francesco PN, Perello M. Brain circuits mediating the orexigenic action of peripheral ghrelin: narrow gates for a vast kingdom. Front Endocrinol (Lausanne). 2015;6:44.
pubmed: 25870587
doi: 10.3389/fendo.2015.00044
Koob GF. A role for brain stress systems in addiction. Neuron. 2008;59:11–34.
pubmed: 18614026
pmcid: 2748830
doi: 10.1016/j.neuron.2008.06.012
Koob GF, Vendruscolo L. Theoretical frameworks and mechanistic aspects of alcohol addiction: alcohol addiction as a reward deficit/stress surfeit disorder. In: Current Topics in Behavioral Neurosciences. Springer, Berlin, Heidelberg. 2023. https://link.springer.com/chapter/10.1007/7854_2023_424 .