Department of Psychology, Reed College, 3203 SE Woodstock Blvd., Portland, OR 97202, United States.
Behav Brain Res. 2012 Jan 1;226(1):96-105. doi: 10.1016/j.bbr.2011.08.037. Epub 2011 Sep 2.
Previous evidence indicates that peripherally administered ghrelin significantly increases corticotropin releasing hormone (CRH) mRNA and serum corticosterone. In addition, intraventricular administration of ghrelin has been reported to elicit anxiety-like behaviors suggesting that the peptide plays a role in mediating neuroendocrine and behavioral responses to stress. In the present study, we characterized the orexigenic, metabolic, and anxiogenic actions of ghrelin following microinjection into the arcuate nucleus (ARN), paraventricular nucleus (PVN), perifornical hypothalamus (PFH), and ventromedial nucleus (VMN). To assess ghrelin's role in anxiogenic behavior, rats were injected with vehicle or 50-800pmol of ghrelin and then placed in an elevated plus maze (EPM) for 10min. Each test was performed as a single trial per animal. In separate behavioral testing we measured the induction of stereotypic behaviors. Doses of 200pmol or higher administered into the ARN and PVN elicited anxiety-like behaviors, including an increased avoidance of the open arms of the EPM. However, in the PFH and VMN, higher doses of ghrelin (400-800pmol) were required to induce anxiety. Ghrelin doses as low as 50pmol stimulated eating and altered energy substrate oxidation (respiratory quotient; RQ) when injected into the ARN and PVN. Injections into the PFH and VMN elicited more modest effects on eating and RQ at doses of 400pmol or greater. Our findings indicate that regions of the hypothalamus appear to be differentially sensitive and responsive to the feeding-stimulant, metabolic, and anxiogenic actions of ghrelin and that the ARN and PVN, in particular, exert a primary role in mediating these effects.
先前的证据表明，外周给予 ghrelin 可显著增加促肾上腺皮质激素释放激素 (CRH) mRNA 和血清皮质酮。此外，已有研究报道脑室给予 ghrelin 会引起类似焦虑的行为，表明该肽在介导神经内分泌和应激反应的行为反应中发挥作用。在本研究中，我们研究了 ghrelin 微注射到弓状核 (ARH)、室旁核 (PVN)、穹窿下区 (PFH) 和腹内侧核 (VMN) 后产生的食欲刺激、代谢和焦虑作用。为了评估 ghrelin 在焦虑行为中的作用，将载体或 50-800pmol 的 ghrelin 注射到大鼠体内，然后将其放入高架十字迷宫 (EPM) 中 10min。每个测试都是针对每个动物进行的单次试验。在单独的行为测试中，我们测量了刻板行为的诱导。200pmol 或更高剂量的 ghrelin 注射到 ARN 和 PVN 会引起类似焦虑的行为，包括增加对 EPM 开放臂的回避。然而，在 PFH 和 VMN 中，需要更高剂量的 ghrelin (400-800pmol) 才能引起焦虑。当 ghrelin 注射到 ARN 和 PVN 时，低至 50pmol 的剂量即可刺激进食并改变能量底物氧化 (呼吸商；RQ)。在 PFH 和 VMN 中，只有当注射剂量为 400pmol 或更高时，才会对进食和 RQ 产生更为温和的影响。我们的研究结果表明，下丘脑的不同区域对 ghrelin 的促食、代谢和焦虑作用可能具有不同的敏感性和反应性，特别是 ARN 和 PVN 可能在介导这些作用中发挥主要作用。
