Requirement of central ghrelin signaling for alcohol reward

被引：331

作者：

Jerlhag, Elisabet ^{[1
]}

Egecioglu, Emil ^{[2
]}

Landgren, Sara ^{[1
]}

Salome, Nicolas ^{[2
]}

Heilig, Markus ^{[3
]}

Moechars, Diederik ^{[4
]}

Datta, Rakesh ^{[5
]}

Perrissoud, Daniel ^{[6
]}

Dickson, Suzanne L. ^{[2
]}

Engel, Jorgen A. ^{[1
]}

机构：

[1] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Pharmacol Sect, SE-40530 Gothenburg, Sweden

[2] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Sect Physiol Endocrinol, SE-40530 Gothenburg, Sweden

[3] NIAAA, Bethesda, MD 20892 USA

[4] Johnson & Johnson Pharmaceut Res & Dev, B-2340 Beerse, Belgium

[5] Ipsen Biomeasure Inc, Milford, MA 01757 USA

[6] Aeterna Zentaris, D-60314 Frankfurt, Germany

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2009年 / 106卷 / 27期

关键词：

appetite; ethanol; GHS-R1A; mesolimbic dopamine system; reinforcing; HORMONE SECRETAGOGUE RECEPTOR; STIMULATES LOCOMOTOR-ACTIVITY; CONDITIONED PLACE PREFERENCE; NUCLEUS-ACCUMBENS; DOPAMINE-OVERFLOW; FOOD-INTAKE; RATS; APPETITE; ETHANOL; BRAIN;

D O I：

10.1073/pnas.0812809106

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The stomach-derived hormone ghrelin interacts with key CNS circuits regulating energy balance and body weight. Here we provide evidence that the central ghrelin signaling system is required for alcohol reward. Central ghrelin administration (to brain ventricles or to tegmental areas involved in reward) increased alcohol intake in a 2-bottle (alcohol/water) free choice limited access paradigm in mice. By contrast, central or peripheral administration of ghrelin receptor (GHS-R1A) antagonists suppressed alcohol intake in this model. Alcohol-induced locomotor stimulation, accumbal dopamine release and conditioned place preference were abolished in models of suppressed central ghrelin signaling: GHS-R1A knockout mice and mice treated with 2 different GHS-R1A antagonists. Thus, central ghrelin signaling, via GHS-R1A, not only stimulates the reward system, but is also required for stimulation of that system by alcohol. Our data suggest that central ghrelin signaling constitutes a potential target for treatment of alcohol-related disorders.

引用

页码：11318 / 11323

页数：6

共 45 条

[31] Toward potent ghrelin receptor ligands based on trisubstituted 1,2,4-triazole structure.: 2.: Synthesis and pharmacological in vitro and in vivo evaluations [J].

Moulin, Aline ;

Demange, Luc ;

Berge, Gilbert ;

Gagne, Didier ;

Ryan, Joanne ;

Mousseaux, Delphine ;

Heitz, Annie ;

Perrissoud, Daniel ;

Locatelli, Vittorio ;

Torsello, Antonio ;

Galleyrand, Jean-Claude ;

Fehrentz, Jean-Alain ;

Martinez, Jean .

JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (23) :5790-5806

[32] Ghrelin induces feeding in the mesolimbic reward pathway between the ventral tegmental area and the nucleus accumbens [J].

Naleid, AM ;

Grace, MK ;

Cummings, DE ;

Levine, AS .

PEPTIDES, 2005, 26 (11) :2274-2279

[33] Simultaneous deletion of ghrelin and its receptor increases motor activity and energy expenditure [J].

Pfluger, Paul T. ;

Kirchner, Henriette ;

Guennel, Susanne ;

Schrott, Brigitte ;

Perez-Tilve, Diego ;

Fu, Sheng ;

Benoit, Stephen C. ;

Horvath, Tamas ;

Joost, Hans-Georg ;

Wortley, Katherine E. ;

Sleeman, Mark W. ;

Tschoep, Matthias H. .

AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2008, 294 (03) :G610-G618

[34] Anorexigenic and electrophysiological actions of novel ghrelin receptor (GHS-R1A) antagonists in rats [J].

Salome, Nicolas ;

Haage, David ;

Perrissoud, Daniel ;

Moulin, Aline ;

Demange, Luc ;

Egecioglu, Emil ;

Fehrentz, Jean-Alain ;

Martinez, Jean ;

Dickson, Suzanne L. .

EUROPEAN JOURNAL OF PHARMACOLOGY, 2009, 612 (1-3) :167-173

[35] Behavioural assessment of drug reinforcement and addictive features in rodents: an overview [J].

Sanchis-Segura, Carles ;

Spanagel, Rainer .

ADDICTION BIOLOGY, 2006, 11 (01) :2-38

[36] Orexigenic peptides and alcohol intake: Differential effects of orexin, galanin, and ghrelin [J].

Schneider, Eve R. ;

Rada, Pedro ;

Darby, Ryan D. ;

Leibowitz, Sarah F. ;

Hoebel, Bartley G. .

ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 2007, 31 (11) :1858-1865

[37] Deletion of ghrelin impairs neither growth nor appetite [J].

Sun, YX ;

Ahmed, S ;

Smith, RG .

MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (22) :7973-7981

[38] Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor [J].

Sun, YX ;

Wang, P ;

Zheng, H ;

Smith, RG .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (13) :4679-4684

[39] Correlation between serum ghrelin levels and cocaine-seeking behaviour triggered by cocaine-associated conditioned stimuli in rats [J].

Tessari, Michela ;

Catalano, Antonio ;

Pellitteri, Michele ;

Di Francesco, Carla ;

Marini, Francesca ;

Gerrard, Philip A. ;

Heidbreder, Christian A. ;

Melotto, Sergio .

ADDICTION BIOLOGY, 2007, 12 (01) :22-29

[40] Ghrelin induces adiposity in rodents [J].

Tschöp, M ;

Smiley, DL ;

Heiman, ML .

NATURE, 2000, 407 (6806) :908-913

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