Behavioral Neuroscience Program, Department of Psychology, Texas A&M University, College Station, TX 77843-4235, USA.
Addict Biol. 2012 Sep;17(5):908-19. doi: 10.1111/j.1369-1600.2011.00392.x. Epub 2011 Oct 21.
Ghrelin (GHR) is an orexigenic gut peptide that interacts with brain ghrelin receptors (GHR-Rs) to promote food intake. Recent research suggests that GHR acts as a modulator of motivated behavior, suggesting a direct influence of GHR on brain reinforcement circuits. In the present studies, we investigated the role of GHR and GHR-Rs in brain reinforcement function. Pharmacological magnetic resonance imaging was used to spatially resolve the functional activation produced by systemic administration of an orexigenic GHR dose. The imaging data revealed a focal activation of a network of subcortical structures that comprise brain reinforcement circuits-ventral tegmental area, lateral hypothalamus and nucleus accumbens. We next analyzed whether brain reinforcement circuits require functional GHR-Rs. To this purpose, wild-type (WT) or mutant rats sustaining N-ethyl-N-nitrosourea-induced knockout of GHR-Rs (GHR-R null rats) were implanted with stimulating electrodes aimed at the lateral hypothalamus, shaped to respond for intracranial self-stimulation (ICSS) and then tested using a rate-frequency procedure to examine ICSS response patterns. WT rats were readily shaped using stimulation intensities of 75 µA, whereas GHR-R null rats required 300 µA for ICSS shaping. No differences in rate-frequency curves were noted for WT rats at 75 µA and GHR-R null rats at 300 µA. When current intensity was lowered to 100 µA, GHR-R null rats did not respond for ICSS. Taken collectively, these data suggest that systemic GHR can activate mesolimbic dopaminergic areas, and highlight a facilitative role of GHR-Rs on the activity of brain reinforcement systems.
胃饥饿素（GHR）是一种促进食欲的肠肽，它与大脑胃饥饿素受体（GHR-R）相互作用，促进食物摄入。最近的研究表明，GHR 作为动机行为的调节剂发挥作用，表明 GHR 对大脑强化回路有直接影响。在本研究中，我们研究了 GHR 和 GHR-Rs 在大脑强化功能中的作用。使用药理学磁共振成象术来空间分辨系统给予促食欲的 GHR 剂量所产生的功能激活。成像数据显示，一组包括大脑强化回路（腹侧被盖区、外侧下丘脑和伏隔核）的皮质下结构的焦点激活。我们接下来分析了大脑强化回路是否需要功能性 GHR-Rs。为此，我们对野生型（WT）或突变为 N-乙基-N-亚硝脲诱导的 GHR-Rs 缺失（GHR-R 缺失大鼠）的大鼠进行了植入，其电极定位于外侧下丘脑，形状为响应颅内自我刺激（ICSS），然后使用率频率程序进行测试，以检查 ICSS 反应模式。WT 大鼠很容易用 75 µA 的刺激强度进行造型，而 GHR-R 缺失大鼠则需要 300 µA 进行 ICSS 造型。在 75 µA 时，WT 大鼠和 300 µA 时的 GHR-R 缺失大鼠的率频率曲线没有差异。当电流强度降低到 100 µA 时，GHR-R 缺失大鼠不会对 ICSS 做出反应。总的来说，这些数据表明，系统 GHR 可以激活中脑边缘多巴胺能区域，并突出 GHR-Rs 对大脑强化系统活性的促进作用。
