THE INTRIGUING LIGAND-DEPENDENT AND LIGAND-INDEPENDENT ACTIONS OF THE GROWTH HORMONE SECRETAGOGUE RECEPTOR ON REWARD-RELATED BEHAVIORS. (January 2021)

• Record Type: Journal Article
• Authors: Cornejo, María P.; Mustafá, Emilio R.; Barrile, Franco; Cassano, Daniela; De Francesco, Pablo N.; Raingo, Jesica; Perello, Mario
• Is Part Of: Neuroscience and biobehavioral reviews. Volume 120(2021)
• Page Start: 401
• Page End: 416
• Publication Date: 2021-01
• Subjects: 5HT serotonin -- Acb nucleus accumbens -- Ach acetylcholine -- AMPA α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid -- AgRP agouti-related protein -- AP area postrema -- ARC arcuate nucleus -- CA cornu ammonis (Ammon's horn) -- cAMP cyclic adenosine monophosphate -- D1R dopamine 1 receptor -- D2R dopamine 2 receptor -- DA dopamine -- DG dentate gyrus -- DR dorsal raphe -- ERK1/2 extracellular signal-regulated kinases 1/2 -- GABA γ-aminobutyric acid -- GHSR growth hormone secretagogue receptor -- GPCR Gprotein-coupled receptor -- IP3 inositol 1, 4, 5-trisphosphate -- LDTg laterodorsal tegmental area -- LEAP2 liver-expressed antimicrobial peptide 2 -- LHA lateral hypothalamic area -- mPFC medial prefrontal cortex -- NMDA N-methyl-D-aspartate -- NTS nucleus of the solitary tract -- OFC orbitofrontal cortex -- OT olfactory tubercle -- PBN parabrachial nucleus -- PVH hypothalamic paraventricular nucleus -- SNC substantia nigra pars compacta -- SuM supramammilary nucleus -- VOCC voltage-operated calcium channels -- VTA ventral tegmental area; GHSR -- ghrelin -- LEAP2 -- constitutive GHSR activity -- reward-related behaviors; Psychophysiology -- Periodicals; Human behavior -- Periodicals; Animal behavior -- Periodicals; Neurology -- Periodicals; Behavior -- Periodicals; Ethology -- Periodicals; Neurology -- Periodicals; Psychophysiologie -- Périodiques; Comportement humain -- Périodiques; Animaux -- Mœurs et comportement -- Périodiques; Neurologie -- Périodiques; Animal behavior; Human behavior; Neurology; Psychophysiology; Periodicals; Electronic journals; 573.8
• DOI: 10.1016/j.neubiorev.2020.10.017
• Languages: English
• ISSNs: 0149-7634

Abstract

Highlights: GHSR displays ligand-dependent and ligand-independent actions. GHSR regulates the activity of the dopamine mesocorticolimbic pathway. GHSR enhances reward-related behaviors towards palatable stimuli and drugs of abuse. Abstract: The growth hormone secretagogue receptor (GHSR) is a G-protein-coupled receptor (GPCR) highly expressed in the brain, and also in some peripheral tissues. GHSR activity is evoked by the stomach-derived peptide hormone ghrelin and abrogated by the intestine-derived liver-expressed antimicrobial peptide 2 (LEAP2). In vitro, GHSR displays ligand-independent actions, including a high constitutive activity and an allosteric modulation of other GPCRs. Beyond its neuroendocrine and metabolic effects, cumulative evidence shows that GHSR regulates the activity of the mesocorticolimbic pathway and modulates complex reward-related behaviors towards different stimuli. Here, we review current evidence indicating that ligand-dependent and ligand-independent actions of GHSR enhance reward-related behaviors towards appetitive stimuli and drugs of abuse. We discuss putative neuronal networks and molecular mechanisms that GHSR would engage to modulate such reward-related behaviors. Finally, we briefly discuss imaging studies showing that ghrelin would also regulate reward processing in humans. Overall, we conclude that GHSR is a key regulator of the mesocorticolimbic pathway that influences its activity and, consequently, modulates reward-related behaviors via ligand-dependent and ligand-independent actions.