PACAP in the BNST Produces Anorexia and Weight Loss in Male and Female Rats
PACAP in the BNST Produces Anorexia and Weight Loss in Male and Female Rats
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DOI：
10.1038/npp.2014.8
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发表时间：
2014-06-01
影响因子：
7.6
通讯作者：
Hammack, Sayamwong E.
中科院分区：
文献类型：
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作者：
Kocho-Schellenberg, Margaret;Lezak, Kimberly R.;Hammack, Sayamwong E.
最近的基因关联研究有牵连的垂体腺苷酸环化酶激活肽（PACAP）系统在一些精神疾病与应激暴露，我们认为，许多行为的后果，反复应激暴露可能取决于表达PACAP在床核的终纹（BNST）。应激系统激活的一个行为后果可能是厌食症和随后的体重减轻，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症状态相关。因此，我们研究了BNST PACAP输注后食物和水摄入量以及体重减轻的调节。BNST PACAP 38在输注后的前24小时内剂量依赖性地降低体重以及食物和水的摄入量。由于不同的BNST子区域差异调节应激反应，我们进一步研究了PACAP 38在前部或后部BNST中的作用。前部BNST PACAP 38输注未改变体重增加，而后部PACAP 38输注导致体重减轻。注入侧脑室的PACAP 38没有改变体重，这表明BNST注入的PACAP的作用不是通过渗漏到脑室系统来介导的。这些数据表明，PACAP受体激活后BNST亚区可以产生厌食症和体重减轻，并证实了越来越多的数据暗示中央PACAP激活介导的压力暴露的后果。
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.