Kocho-Schellenberg Margaret, Lezak Kimberly R, Harris Olivia M, Roelke Erin, Gick Niklas, Choi Inyop, Edwards Shaquille, Wasserman Emily, Toufexis Donna J, Braas Karen M, May Victor, Hammack Sayamwong E
Department of Psychology, University of Vermont, Burlington, USA.
Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, USA.
Neuropsychopharmacology. 2014 Jun;39(7):1614-23. doi: 10.1038/npp.2014.8. Epub 2014 Jan 17.
Recent gene association studies have implicated pituitary adenylate cyclase-activating peptide (PACAP) systems in several psychiatric disorders associated with stressor exposure, and we have argued that many of the behavioral consequences of repeated stressor exposure may depend on the expression of PACAP in the bed nucleus of the stria terminalis (BNST). One behavioral consequence of the activation of stress systems can be anorexia and subsequent weight loss, and both the activation of central PACAP systems as well as neuronal activity in the BNST have also been associated with anorexic states in rodents. Hence, we investigated the regulation of food and water intake and weight loss following BNST PACAP infusion. BNST PACAP38 dose-dependently decreased body weight, as well as food and water intake in the first 24 h following infusion. Because different BNST subregions differentially regulate stress responding, we further examined the effects of PACAP38 in either the anterior or posterior BNST. Anterior BNST PACAP38 infusion did not alter weight gain, whereas posterior PACAP38 infusion resulted in weight loss. PACAP38 infused into the lateral ventricles did not alter weight, suggesting that the effects of BNST-infused PACAP were not mediated by leakage into the ventricular system. These data suggest that PACAP receptor activation in posterior BNST subregions can produce anorexia and weight loss, and corroborate growing data implicating central PACAP activation in mediating the consequences of stressor exposure.
最近的基因关联研究表明，垂体腺苷酸环化酶激活肽（PACAP）系统与几种与应激源暴露相关的精神疾病有关，并且我们认为反复应激源暴露的许多行为后果可能取决于终纹床核（BNST）中PACAP的表达。应激系统激活的一个行为后果可能是厌食和随后的体重减轻，并且中枢PACAP系统的激活以及BNST中的神经元活动也与啮齿动物的厌食状态有关。因此，我们研究了BNST注入PACAP后食物和水的摄入量以及体重减轻的调节情况。BNST PACAP38在注入后的头24小时内剂量依赖性地降低了体重以及食物和水的摄入量。由于不同的BNST亚区域对应激反应的调节不同，我们进一步研究了PACAP38在前BNST或后BNST中的作用。注入前BNST PACAP38不会改变体重增加，而注入后PACAP38会导致体重减轻。注入侧脑室的PACAP38不会改变体重，这表明注入BNST的PACAP的作用不是由漏入脑室系统介导的。这些数据表明，后BNST亚区域中的PACAP受体激活可导致厌食和体重减轻，并证实了越来越多的数据表明中枢PACAP激活在介导应激源暴露的后果中起作用。
