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 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.

生长激素促分泌素受体（GHSR）是在大脑以及某些外围组织中高度表达的G蛋白偶联受体（GPCR）。GHSR活性由胃源性肽激素ghrelin引起，并由肠源性肝抗菌肽2（LEAP2）消除。体外GHSR显示出不依赖配体的作用，包括高本构活性和其他GPCR的变构调节。除了其神经内分泌和代谢作用外，累积证据还表明，GHSR调节中皮层皮质途径的活性，并调节针对不同刺激的复杂奖赏相关行为。在这里，我们审查了当前的证据，表明GHSR的配体依赖性和配体依赖性行为增强了对食欲刺激和滥用药物的奖励相关行为。我们讨论了推测的神经元网络和GHSR参与调节此类奖励相关行为的分子机制。最后，我们简要讨论成像研究，这些研究表明生长素释放肽也可以调节人类的奖赏过程。总体，