Rada Pedro, Avena Nicole M, Leibowitz Sarah F, Hoebel Bartley G
Department of Psychology, Princeton University, Princeton, NJ 08544, USA.
Alcohol. 2004 Jun;33(2):91-7. doi: 10.1016/j.alcohol.2004.05.002.
Ethanol intake stimulates expression of galanin in several hypothalamic sites, including the paraventricular nucleus. Because injection of galanin in the paraventricular nucleus induces eating, we hypothesized that galanin might also affect ethanol intake. Rats were given ad libitum access to 4% ethanol for 4 weeks and assigned to one of two groups according to levels of ethanol consumption: high levels (>1.5 g/ kg/day) or low levels (<1.0 g/kg/day). In Experiment 1, galanin (1.0 nmol) or Ringer's solution was injected unilaterally into the paraventricular nucleus, with food and water absent during the first 4 h. Galanin significantly increased ethanol intake only in rats that drank high levels of ethanol. In Experiment 2, injection of galanin (0.5 and 1.0 nmol) in the paraventricular nucleus dose-dependently increased ethanol intake with food and water available. The higher dose was also effective in eliciting ethanol intake when tested with food and water absent. In Experiment 3, a test of receptor specificity was provided by injecting rats with the galanin antagonist M-40 (0.5 nmol) or Ringer's solution. Injection of M-40 in the paraventricular nucleus significantly decreased ethanol consumption. In Experiment 4, an anatomic control, with galanin injected 2 mm dorsal to the paraventricular nucleus in the same animals, caused no change in ethanol intake. In conclusion, injection of galanin in the paraventricular nucleus, at a dose known to induce feeding, acted by means of a galanin receptor to potentiate intake of 4% ethanol, even with food and water available as alternate sources of calories and fluid, respectively. Because ethanol can increase expression of galanin mRNA in the paraventricular nucleus, this could set the stage for a positive feedback loop between galanin and ethanol intake.
乙醇摄入会刺激包括室旁核在内的几个下丘脑部位的甘丙肽表达。由于向室旁核注射甘丙肽会诱导进食，我们推测甘丙肽可能也会影响乙醇摄入。给大鼠随意提供4%的乙醇，持续4周，并根据乙醇摄入量将其分为两组：高摄入量组（>1.5克/千克/天）或低摄入量组（<1.0克/千克/天）。在实验1中，在最初4小时不给食物和水的情况下，将甘丙肽（1.0纳摩尔）或林格氏液单侧注入室旁核。甘丙肽仅在饮用高剂量乙醇的大鼠中显著增加了乙醇摄入量。在实验2中，在有食物和水供应的情况下，向室旁核注射甘丙肽（0.5和1.0纳摩尔），乙醇摄入量呈剂量依赖性增加。在不给食物和水的情况下进行测试时，较高剂量也能有效引发乙醇摄入。在实验3中，通过给大鼠注射甘丙肽拮抗剂M-40（0.5纳摩尔）或林格氏液来进行受体特异性测试。向室旁核注射M-40显著降低了乙醇消耗量。在实验4中，作为解剖学对照，在同一动物的室旁核背侧2毫米处注射甘丙肽，乙醇摄入量没有变化。总之，向室旁核注射已知能诱导进食剂量的甘丙肽，通过甘丙肽受体作用增强了4%乙醇的摄入量，即使分别有食物和水作为热量和液体的替代来源。由于乙醇可增加室旁核中甘丙肽mRNA的表达，这可能为甘丙肽与乙醇摄入之间的正反馈回路奠定基础。
